Is GRID2 p.Ala317Val (c.950C>T) pathogenic?

GRID2 p.Ala317Val (c.950C>T) is classified Conflicting classifications of pathogenicity in GRID2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-06-27). AlphaMissense: likely benign (0.1275); Ultra-rare (popmax 0.0385%, sas); Associated with Inborn genetic diseases.

What condition is associated with GRID2 p.Ala317Val (c.950C>T)?

GRID2 p.Ala317Val (c.950C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRID2 p.Ala317Val (c.950C>T) in the general population?

GRID2 p.Ala317Val (c.950C>T) is ultra-rare (popmax 0.0385%, sas) (gnomAD).

What do computational predictors say about GRID2 p.Ala317Val (c.950C>T)?

AlphaMissense predicts likely benign (score 0.1275) — an in-silico prediction, not a clinical call.

GRID2 p.Ala317Val

c.950C>T · rs538573274 · VCV2621577

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1275 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0385%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1275	likely benign
REVEL	0.205	benign-leaning
SaProt	LLR -5.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.53, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 920 kb · p 0.22 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0385% South Asian · 35/90,952 alleles

Filtering AF 0.0284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00217% 35/1,610,404 alleles · ultra-rare exomes 34/1,458,192 · genomes 1/152,212 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GRID2
Protein: p.Ala317Val
Coding: c.950C>T
MANE Select: NM_001510
dbSNP: rs538573274
Type: single nucleotide variant
Location: chr4:93216898 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.07 · 6 PDB
Residue 317: an α-helix; the 'interaction with cbln1 homotrimer' region

Full GRID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRID2 p.Ala317Ser Uncertain significance ★ ⚠ same residue
GRID2 p.Ala654Thr Pathogenic/Likely pathogenic ★★ same condition
GRID2 p.Ala196Glu Uncertain significance ★★ ⚠ same condition
GRID2 p.Ala21Val Uncertain significance ★★ ⚠ same condition
GRID2 p.Ala574Ser Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg229Gln Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg297Gln Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg439Leu Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/grid2-p-ala317val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown