NM_001101426.4:c.55A>C

Variant names:

• chr7-16421268-T-G
• rs7782939
• NM_001101426.4:c.55A>C
• CRPPA p.Ser19Arg

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-5 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -5 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_StrongB3_Supporting

The NM_001101426.4(CRPPA):c.55A>C (p.Ser19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.304 (AC=394,087) in the gnomAD database across 1,297,340 control chromosomes, including 60,694 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.378. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★★). The variant has been observed in cBioPortal in 1 sample across 1 study and 1 cancer type; somatic enrichment level: NONE (Observed in at most one deduplicated cBioPortal case.). This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

• Frequency:
  • Genomes: 𝑓 0.30 (6867 hom., cov: 33)
  • Exomes 𝑓: 0.30 (53827 hom.)
• Consequence: CRPPA NM_001101426.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -1.69
• Publications: 16 publications found

Genes affected

CRPPA (HGNC:37276): (CDP-L-ribitol pyrophosphorylase A) This gene encodes a 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase-like protein. Mutations in this gene are the cause of Walker-Warburg syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, May 2012]

CRPPA Gene-Disease associations (from GenCC):

• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• myopathy caused by variation in CRPPA

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2U

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• congenital muscular dystrophy without intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• muscular dystrophy-dystroglycanopathy, type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000272537 (HGNC:):

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -5 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.378 — exceeds 1% threshold (B1 applied)
	B3Computational evidence does not support deleterious effect		Computational evidence does not support a deleterious effect; Missense variant — primary computational scorer does not support an oncogenic/deleterious effect; supports B3

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001101426.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CRPPA NM_001101426.4	MANE Select	c.55A>C p.Ser19Arg	missense	Exon 1 of 10	Prot: NP_001094896.1 UniProt:
	CRPPA NM_001368197.1		c.55A>C p.Ser19Arg	missense	Exon 1 of 9	Prot: NP_001355126.1
	CRPPA NM_001101417.4		c.55A>C p.Ser19Arg	missense	Exon 1 of 9	Prot: NP_001094887.1 UniProt:

CRPPA NM_001101426.4

MANE Select

HGVSc / HGVSpc.55A>Cp.Ser19Arg

Exon rankExon 1 of 10

missense

Prot: NP_001094896.1UniProt: A4D126-1

CRPPA NM_001368197.1

HGVSc / HGVSpc.55A>Cp.Ser19Arg

Exon rankExon 1 of 9

missense

Prot: NP_001355126.1

CRPPA NM_001101417.4

HGVSc / HGVSpc.55A>Cp.Ser19Arg

Exon rankExon 1 of 9

missense

Prot: NP_001094887.1UniProt: A0A140VJM1A4D126-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	CRPPA ENST00000407010.7	TSL:5MANE Select	c.55A>C p.Ser19Arg	missense	Exon 1 of 10	Prot: ENSP00000385478.2 UniProt:
	CRPPA ENST00000399310.3	TSL:1	c.55A>C p.Ser19Arg	missense	Exon 1 of 9	Prot: ENSP00000382249.3 UniProt:
	CRPPA ENST00000856526.1		c.55A>C p.Ser19Arg	missense	Exon 1 of 8	Prot: ENSP00000526585.1 UniProt:

CRPPA ENST00000407010.7

TSL:5MANE Select

HGVSc / HGVSpc.55A>Cp.Ser19Arg

Exon rankExon 1 of 10

missense

Prot: ENSP00000385478.2UniProt: A4D126-1

CRPPA ENST00000399310.3

TSL:1

HGVSc / HGVSpc.55A>Cp.Ser19Arg

Exon rankExon 1 of 9

missense

Prot: ENSP00000382249.3UniProt: A4D126-2

CRPPA ENST00000856526.1

HGVSc / HGVSpc.55A>Cp.Ser19Arg

Exon rankExon 1 of 8

missense

Prot: ENSP00000526585.1UniProt: A0ACI8QS87

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 6 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.299	AC:45300	Hom:6873	AN:151428	Cov:33
GnomAD2 exomes	AF: 0.257	AC:3585	Hom:	AN:13926	Cov:
GnomAD4 exome	AF: 0.304	AC:348776	Hom:53827	AN:1145802	Cov:34
GnomAD4 genome	AF: 0.299	AC:45311	Hom:6867	AN:151538	Cov:33
TOPMed (Bravo)	AF: 0.296	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.212	AC:7251	Hom:1070	AN:34150	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.291	AC:682	Hom:92	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.304	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.317	AC:95	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.337	AC:1170	Hom:	AN:3464	Cov:
Korea4K (4,157 Koreans)	AF: 0.275	AC:1972	Hom:	AN:7174	Cov:
Qatari Genome	AF: 0.295	AC:52	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.277	AC:33747	Hom:4753	AN:121754	Cov:
Turkish Variome	AF: 0.276	AC:426	Hom:66	AN:1546	Cov:
UK10K	AF: 0.318	AC:2406	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.292	AC:2618	Hom:372	AN:8960	Cov:

Showing 16 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.330	39170	118816	0.346	62020	179310

Showing 1 cohortAllele count / allele number. AF is computed from the counts for ASC (not provided by the source).

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	1	Congenital Muscular Dystrophy, alpha-dystroglycan related (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (1)
-	-	1	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7;C5190987:Autosomal recessive limb-girdle muscular dystrophy type 2U (1)
-	-	1	not provided (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	5.2
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	3.4
DANN	Benign	0.79
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.062	N
FuncVEP CTI	Benign	0.0019
GPN-Star LLR	N/A	-1.1
GPN-Star score	N/A	1.1
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.1	T
Mutation Taster	N/A	100/0	polymorphism (auto)
MutationAssessor	Benign	0.0	N
PhyloP100	Benign	-1.7
popEVE	Benign	-3.0
PrimateAI	Uncertain	0.75	T
PromoterAI	N/A	0.12	Neutral
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.14
Sift	Benign	0.88	T
Sift4G	Benign	0.66	T
Varity_R	N/A	0.046
VESM-3B	Benign	-2.4

Showing 28 of 28 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs7782939;

hg19: chr7-16460893;

COSMIC: COSV67907237;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar