Is GRIN1 p.Ala331Val (c.992C>T) pathogenic?

GRIN1 p.Ala331Val (c.992C>T) is classified Conflicting classifications of pathogenicity in GRIN1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0768); Very rare (popmax 0.00223%, eas); Associated with neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant.

How common is GRIN1 p.Ala331Val (c.992C>T) in the general population?

GRIN1 p.Ala331Val (c.992C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about GRIN1 p.Ala331Val (c.992C>T)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

GRIN1 p.Ala331Val

Q: What condition is associated with GRIN1 p.Ala331Val (c.992C>T)?

GRIN1 p.Ala331Val (c.992C>T) is associated with neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (ClinVar).

c.992C>T · rs201324316 · VCV833520

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -5.53	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 5.7	GERP 1.1, phastCons 1
Overall
CADD	24.1	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 0.00223% East Asian · 1/44,894 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,613,362 alleles · very rare exomes 18/1,461,200 · genomes 1/152,162 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,894
South Asian	0.0022%	45,539
European (non-Finnish)	0.00136%	73,747

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: GRIN1
Protein: p.Ala331Val
Coding: c.992C>T
MANE Select: NM_007327
dbSNP: rs201324316
Type: single nucleotide variant
Location: chr9:137158402 (GRCh38)
Structure: AlphaFold pLDDT 44.02
Residue 331: the 'disordered' region

Full GRIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRIN1 p.Ala331= Likely benign ★★ same residue
GRIN1 p.Ala331Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
GRIN1 p.Ala331Thr Uncertain significance ★ ⚠ same residue
GRIN1 p.Arg659Gln Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Arg659Trp Pathogenic ★★ same condition
GRIN1 p.Arg794Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
GRIN1 p.Arg844Cys Pathogenic/Likely pathogenic ★★ same condition
GRIN1 p.Arg844Leu Pathogenic/Likely pathogenic ★★ 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/grin1-p-ala331val (accessed [today's date]).

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