NM_018836.4:c.568G>C

Variant names:

• chr1-4712438-G-C
• rs764876909
• NM_018836.4:c.568G>C
• AJAP1 p.Glu190Gln

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 (ACMG Germline Pathogenicity v2019). PM2_SupportingBS2BP4_Moderate

The NM_018836.4(AJAP1):c.568G>C (p.Glu190Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.00000619 (AC=9) in the gnomAD database across 1,454,590 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000465. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.E190K: Uncertain_significance (ClinVar VariationId 2256850, 1 star)

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: AJAP1 NM_018836.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42
• Publications: 1 publications found

Genes affected

AJAP1 (HGNC:30801): (adherens junctions associated protein 1) Enables beta-catenin binding activity. Involved in negative regulation of cell-matrix adhesion; negative regulation of wound healing; and regulation of polarized epithelial cell differentiation. Located in several cellular components, including adherens junction; basolateral plasma membrane; and cell-cell contact zone. [provided by Alliance of Genome Resources, Jul 2025]

AJAP1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Rare in gnomAD for AD/XL gene (popmax AF below threshold) — PM2 Supporting; GnomAD popmax AF = 0.0000465 — borderline rare for AD/XL gene (threshold 0.0001) — PM2 supporting.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).
	BS2Observed in healthy adult		Pure AD gene with cumulative gnomAD AC ≥5 — observed in healthy adults (BS2); GnomAD homozygous count = 0.; Cumulative gnomAD AC = 9 (pure AD gene, not AR).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_018836.4. 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
	AJAP1 NM_018836.4	MANE Select	c.568G>C p.Glu190Gln	missense	Exon 2 of 6	Prot: NP_061324.1 UniProt:
	AJAP1 NM_001042478.2		c.568G>C p.Glu190Gln	missense	Exon 2 of 6	Prot: NP_001035943.1 UniProt:

AJAP1 NM_018836.4

MANE Select

HGVSc / HGVSpc.568G>Cp.Glu190Gln

Exon rankExon 2 of 6

missense

Prot: NP_061324.1UniProt: Q9UKB5

AJAP1 NM_001042478.2

HGVSc / HGVSpc.568G>Cp.Glu190Gln

Exon rankExon 2 of 6

missense

Prot: NP_001035943.1UniProt: Q9UKB5

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	AJAP1 ENST00000378191.5	TSL:1MANE Select	c.568G>C p.Glu190Gln	missense	Exon 2 of 6	Prot: ENSP00000367433.3 UniProt:
	AJAP1 ENST00000378190.7	TSL:5	c.568G>C p.Glu190Gln	missense	Exon 2 of 6	Prot: ENSP00000367432.3 UniProt:
	AJAP1 ENST00000880749.1		c.568G>C p.Glu190Gln	missense	Exon 2 of 5	Prot: ENSP00000550808.1 UniProt:

AJAP1 ENST00000378191.5

TSL:1MANE Select

HGVSc / HGVSpc.568G>Cp.Glu190Gln

Exon rankExon 2 of 6

missense

Prot: ENSP00000367433.3UniProt: Q9UKB5

AJAP1 ENST00000378190.7

TSL:5

HGVSc / HGVSpc.568G>Cp.Glu190Gln

Exon rankExon 2 of 6

missense

Prot: ENSP00000367432.3UniProt: Q9UKB5

AJAP1 ENST00000880749.1

HGVSc / HGVSpc.568G>Cp.Glu190Gln

Exon rankExon 2 of 5

missense

Prot: ENSP00000550808.1UniProt: Q9UKB5

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 5 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD2 exomes	AF: 0.0000127	AC:3	Hom:	AN:235578	Cov:
GnomAD4 exome	AF: 0.00000619	AC:9	Hom:0	AN:1454590	Cov:37
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:0	AN:16840	Cov:

Showing 5 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
SCHEMA(Schizophrenia)	0.00	0	100336	0.0000111	2	180132

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

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Pathogenic	23
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.043	T
Eigen	Benign	0.035
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.86	D
FuncVEP CTI	Benign	0.066
GPN-Star LLR	N/A	-7.4
GPN-Star score	N/A	7.4
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.83	T
Mutation Taster	N/A	94/6	polymorphism
MutationAssessor	Benign	1.6	L
PhyloP100	Benign	2.4
popEVE	Benign	-3.2
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.092
Sift	Uncertain	0.023	D
Sift4G	Benign	0.088	T
Varity_R	N/A	0.26
VESM-3B	Benign	-6.6

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: rs764876909;

hg19: chr1-4772498;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar