Is GRID1 p.Val380Ala (c.1139T>C) pathogenic?

GRID1 p.Val380Ala (c.1139T>C) is classified Uncertain significance in GRID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.0958); Very rare (popmax 0.000509%, nfe).

How common is GRID1 p.Val380Ala (c.1139T>C) in the general population?

GRID1 p.Val380Ala (c.1139T>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about GRID1 p.Val380Ala (c.1139T>C)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

GRID1 p.Val380Ala

c.1139T>C · VCV3522589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -7.19	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 7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 254 kb · p 0.00028 · regional, not allelic
Overall
CADD	19.61	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 0.000509% European (non-Finnish) · 6/1,179,910 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,998 alleles · very rare exomes 6/1,461,762 · genomes 0/152,236 · 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: GRID1
Protein: p.Val380Ala
Coding: c.1139T>C
MANE Select: NM_017551
Type: single nucleotide variant
Location: chr10:85854590 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.52 · 3 PDB
Residue 380: the 'interaction with cbln1' region

Full GRID1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRID1 p.Ala127Thr Uncertain significance ★★ ⚠ same type
GRID1 p.Ala603Asp Uncertain significance ★★ ⚠ same type
GRID1 p.Arg221Gln Uncertain significance ★★ ⚠ same type
GRID1 p.Arg384Gln Uncertain significance ★★ ⚠ same type
GRID1 p.Arg879His Uncertain significance ★★ ⚠ same type
GRID1 p.Asp307Asn Uncertain significance ★★ ⚠ same type
GRID1 p.Gly716Arg Uncertain significance ★★ ⚠ same type
GRID1 p.Pro120Gln 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/grid1-p-val380ala (accessed [today's date]).

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