Is GRID2 p.Ala650Val (c.1949C>T) pathogenic?

GRID2 p.Ala650Val (c.1949C>T) is classified Likely pathogenic in GRID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-20). AlphaMissense: likely pathogenic (0.9963); Absent from gnomAD v4.1.

How common is GRID2 p.Ala650Val (c.1949C>T) in the general population?

GRID2 p.Ala650Val (c.1949C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRID2 p.Ala650Val (c.1949C>T)?

AlphaMissense predicts likely pathogenic (score 0.9963) — an in-silico prediction, not a clinical call.

GRID2 p.Ala650Val

c.1949C>T · rs2546697855 · VCV1723717

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9963	likely pathogenic ✓ concordant with ClinVar · top 6% in GRID2
REVEL	0.826	moderately pathogenic-leaning
SaProt	LLR -14.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.39	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 548 kb · p 0.0047 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRID2
Protein: p.Ala650Val
Coding: c.1949C>T
MANE Select: NM_001510
dbSNP: rs2546697855
Type: single nucleotide variant
Location: chr4:93490729 (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

Similar variants

GRID2 p.Ala650Pro Uncertain significance ★ ⚠ same residue
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

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-ala650val (accessed [today's date]).

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