SLC2A9 p.Val282Ile

Variant names:

• chr4-9920543-C-T
• rs16890979
• NM_020041.3:c.844G>A
• SLC2A9 p.Val282Ile

Your query was ambiguous. Multiple possible variants found:

• chr4-9920543-C-T
• chr4-9920541-AAC-GAT
• chr4-9920541-AAC-TAT

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_020041.3(SLC2A9):c.844G>A (p.Val282Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The gene SLC2A9 is a tumor suppressor gene (CancerMine: 2 TSG citations). The variant allele was found at a cumulative frequency of 0.229 (AC=370,036) in the gnomAD database across 1,613,968 control chromosomes, including 46,504 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.429. 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 4 samples across 3 studies and 3 cancer types; somatic enrichment level: SUPPORTING_LOW (Observed in a small number of cBioPortal cases.). 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 0.28 (6967 hom., cov: 33)
  • Exomes 𝑓: 0.22 (39537 hom.)
• Consequence: SLC2A9 NM_020041.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.76
• Publications: 147 publications found

Genes affected

SLC2A9 (HGNC:13446): (solute carrier family 2 member 9) This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a significant role in maintaining glucose homeostasis. The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SLC2A9 Gene-Disease associations (from GenCC):

• hypouricemia, renal, 2

  Inheritance: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

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 = 0.429 — 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_020041.3. 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
	SLC2A9 NM_020041.3	MANE Select	c.844G>A p.Val282Ile	missense	Exon 7 of 12	Prot: NP_064425.2
	SLC2A9 NM_001001290.2		c.757G>A p.Val253Ile	missense	Exon 8 of 13	Prot: NP_001001290.1 UniProt:

SLC2A9 NM_020041.3

MANE Select

HGVSc / HGVSpc.844G>Ap.Val282Ile

Exon rankExon 7 of 12

missense

Prot: NP_064425.2

SLC2A9 NM_001001290.2

HGVSc / HGVSpc.757G>Ap.Val253Ile

Exon rankExon 8 of 13

missense

Prot: NP_001001290.1UniProt: Q9NRM0-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	SLC2A9 ENST00000264784.8	TSL:1MANE Select	c.844G>A p.Val282Ile	missense	Exon 7 of 12	Prot: ENSP00000264784.3 UniProt:
	SLC2A9 ENST00000309065.7	TSL:1	c.757G>A p.Val253Ile	missense	Exon 8 of 13	Prot: ENSP00000311383.3 UniProt:
	SLC2A9 ENST00000505104.5	TSL:1	n.878G>A	non_coding_transcript_exon	Exon 8 of 12	Prot:

SLC2A9 ENST00000264784.8

TSL:1MANE Select

HGVSc / HGVSpc.844G>Ap.Val282Ile

Exon rankExon 7 of 12

missense

Prot: ENSP00000264784.3UniProt: Q9NRM0-1

SLC2A9 ENST00000309065.7

TSL:1

HGVSc / HGVSpc.757G>Ap.Val253Ile

Exon rankExon 8 of 13

missense

Prot: ENSP00000311383.3UniProt: Q9NRM0-2

SLC2A9 ENST00000505104.5

TSL:1

HGVSc / HGVSpn.878G>A

Exon rankExon 8 of 12

non_coding_transcript_exon

Prot:

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: 0.282	AC:42936	Hom:6956	AN:152072	Cov:33
GnomAD2 exomes	AF: 0.243	AC:61149	Hom:	AN:251162	Cov:
GnomAD4 exome	AF: 0.224	AC:327053	Hom:39537	AN:1461778	Cov:38
GnomAD4 genome	AF: 0.282	AC:42983	Hom:6967	AN:152190	Cov:33
TOPMed (Bravo)	AF: 0.300	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.248	AC:83850	Hom:11588	AN:338330	Cov:
Local & regional cohorts 11 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.289	AC:677	Hom:106	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.0193	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.233	AC:70	Hom:	AN:300	Cov:
ESP6500 (Exome Variant Server)	AF: 0.286	AC:3724	Hom:	AN:13006	Cov:
GenomeAsia100K	AF: 0.153	AC:532	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.0100	AC:73	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.218	AC:438	Hom:	AN:2010	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.00847	AC:1039	Hom:6	AN:122716	Cov:
Turkish Variome	AF: 0.270	AC:1804	Hom:273	AN:6670	Cov:
UK10K	AF: 0.218	AC:1646	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.0126	AC:113	Hom:1	AN:8960	Cov:

Showing 17 sources

Case/control cohorts

Cohort	Cases			Controls
	AF	AC	AN	AF	AC	AN
ASC(Autism)	0.210 *	2333	11106	0.208 *	3654	17598
BipEx(Bipolar disorder (including schizoaffective))	0.209	5950	28420	0.211	6087	28844
Epi25(Epilepsy)	0.221	9288	41958	0.243	16286	66886
SCHEMA(Schizophrenia)	0.201	24261	120558	0.206	38834	188774

Showing 4 cohortsAllele 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
-	-	3	not provided (3)
-	-	2	Hypouricemia, renal, 2 (2)
-	-	1	not specified (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	9.3
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.5
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.88	D
FuncVEP CTI	Benign	0.14
GPN-Star LLR	N/A	-1.3
GPN-Star score	N/A	1.3
LIST_S2	Benign	0.72	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.98	T
Mutation Taster	N/A	100/0	polymorphism (auto)
MutationAssessor	Uncertain	2.1	M
PhyloP100	Benign	1.8
popEVE	Benign	-3.0
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.47	N
RBP_binding_hub_radar	N/A	0.0
RBP_regulation_power_radar	N/A	1.1
REVEL	Benign	0.23
Sift	Benign	0.16	T
Sift4G	Benign	0.25	T
Varity_R	N/A	0.052
VESM-3B	Benign	-5.8

Showing 29 of 29 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.020	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: rs16890979;

hg19: chr4-9922167;

COSMIC: COSV53316809;

COSMIC: COSV53316809;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar