Is GRID2 p.Asp267Val (c.800A>T) pathogenic?

GRID2 p.Asp267Val (c.800A>T) is classified Uncertain significance in GRID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-13). AlphaMissense: likely pathogenic (0.6228); Absent from gnomAD v4.1; Associated with autosomal recessive spinocerebellar ataxia 18.

What condition is associated with GRID2 p.Asp267Val (c.800A>T)?

GRID2 p.Asp267Val (c.800A>T) is associated with autosomal recessive spinocerebellar ataxia 18 (ClinVar).

How common is GRID2 p.Asp267Val (c.800A>T) in the general population?

GRID2 p.Asp267Val (c.800A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRID2 p.Asp267Val (c.800A>T)?

AlphaMissense predicts likely pathogenic (score 0.6228) — an in-silico prediction, not a clinical call.

GRID2 p.Asp267Val

Q: How is Autosomal recessive cerebellar ataxia-pyramidal signs-nystagmus-oculomotor apraxia syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.800A>T · VCV3363136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6228 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive spinocerebellar ataxia 18

Computational evidence

Protein change
AlphaMissense	0.6228	likely pathogenic
REVEL	0.883	moderately pathogenic-leaning
SaProt	LLR -9.94	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
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	24.0	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.Asp267Val
Coding: c.800A>T
MANE Select: NM_001510
Type: single nucleotide variant
Location: chr4:93216748 (GRCh38)
Gene constraint: LOEUF 0.332 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.07 · 6 PDB
Residue 267: the 'interaction with cbln1 homotrimer' region; an α-helix

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

Disease context

autosomal recessive spinocerebellar ataxia 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive cerebellar ataxia-pyramidal signs-nystagmus-oculomotor apraxia syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

GRID2 p.Asp267Asn Uncertain significance ★★ ⚠ same residue
GRID2 p.Thr649Ala Pathogenic/Likely pathogenic ★★ same condition
GRID2 p.Arg300His Uncertain significance ★★ ⚠ same condition
GRID2 p.Arg367His Uncertain significance ★★ ⚠ same condition
GRID2 p.Asp473Glu Uncertain significance ★★ ⚠ same condition
GRID2 p.Gly391Arg Uncertain significance ★★ ⚠ same condition
GRID2 c.735+21G>C Benign ★★ same condition
GRID2 p.Gly417= Benign ★★ 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-asp267val (accessed [today's date]).

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