Is GRID2 p.Ala21Val (c.62C>T) pathogenic?

GRID2 p.Ala21Val (c.62C>T) is classified Uncertain significance in GRID2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-27). AlphaMissense: likely benign (0.0924); Rare (popmax 0.109%, afr); Associated with Inborn genetic diseases.

What condition is associated with GRID2 p.Ala21Val (c.62C>T)?

GRID2 p.Ala21Val (c.62C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRID2 p.Ala21Val (c.62C>T) in the general population?

GRID2 p.Ala21Val (c.62C>T) is rare (popmax 0.109%, afr) (gnomAD).

What do computational predictors say about GRID2 p.Ala21Val (c.62C>T)?

AlphaMissense predicts likely benign (score 0.0924) — an in-silico prediction, not a clinical call.

GRID2 p.Ala21Val

c.62C>T · rs146789050 · VCV1419994

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0924 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.109%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0924	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.92	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 2.6	GERP 1, phastCons 0.99
Regional constraint	o/e 1.06	unconstrained · MANE · 920 kb · p 0.22 · regional, not allelic
Overall
CADD	18.18	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% African / African-American · 82/74,990 alleles

Filtering AF 0.0903% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0832%

Overall 0.00564% 91/1,612,714 alleles · rare exomes 35/1,460,450 · genomes 56/152,264 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.109%	915
Middle Eastern	0.0165%	6,056
Remaining individualsnot grpmax-eligible	0.00801%	12,492
Admixed American	0.005%	19,997

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.Ala21Val
Coding: c.62C>T
MANE Select: NM_001510
dbSNP: rs146789050
Type: single nucleotide variant
Location: chr4:92304718 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.07 · 6 PDB

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.Ala21Glu Uncertain significance ★ ⚠ same residue
GRID2 p.Ala654Thr Pathogenic/Likely pathogenic ★★ same condition
GRID2 p.Ala196Glu 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
GRID2 p.Arg714Gln 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-ala21val (accessed [today's date]).

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