Is GRID2 p.Asp269Val (c.806A>T) pathogenic?

GRID2 p.Asp269Val (c.806A>T) is classified Uncertain significance in GRID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). AlphaMissense: ambiguous (0.546); Very rare (popmax 0.00834%, amr).

How common is GRID2 p.Asp269Val (c.806A>T) in the general population?

GRID2 p.Asp269Val (c.806A>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about GRID2 p.Asp269Val (c.806A>T)?

AlphaMissense predicts ambiguous (score 0.546) — an in-silico prediction, not a clinical call.

GRID2 p.Asp269Val

c.806A>T · rs1268349440 · VCV1935299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.546	ambiguous
REVEL	0.902	moderately pathogenic-leaning
SaProt	LLR -8.95	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 920 kb · p 0.22 · regional, not allelic
Overall
CADD	25.4	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 0.00834% Admixed American · 5/59,932 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000373% 6/1,609,080 alleles · very rare exomes 4/1,456,908 · genomes 2/152,172 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,986
Remaining individualsnot grpmax-eligible	0.00161%	62,292

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.Asp269Val
Coding: c.806A>T
MANE Select: NM_001510
dbSNP: rs1268349440
Type: single nucleotide variant
Location: chr4:93216754 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.07 · 6 PDB
Residue 269: the 'interaction with cbln1 homotrimer' region; an α-helix

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

Similar variants

GRID2 p.Ala654Thr Pathogenic/Likely pathogenic ★★ same type
GRID2 p.Thr649Ala Pathogenic/Likely pathogenic ★★ same type
GRID2 p.Ala196Glu Uncertain significance ★★ ⚠ same type
GRID2 p.Ala21Val Uncertain significance ★★ ⚠ same type
GRID2 p.Ala574Ser Uncertain significance ★★ ⚠ same type
GRID2 p.Arg229Gln Uncertain significance ★★ ⚠ same type
GRID2 p.Arg297Gln Uncertain significance ★★ ⚠ same type
GRID2 p.Arg300His Uncertain significance ★★ ⚠ same type

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-asp269val (accessed [today's date]).

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