Is GRIN1 p.Arg337= (c.1011C>T) pathogenic?

GRIN1 p.Arg337= (c.1011C>T) is classified Likely benign in GRIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-10). Very rare (popmax 0.00223%, eas); Associated with neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant.

How common is GRIN1 p.Arg337= (c.1011C>T) in the general population?

GRIN1 p.Arg337= (c.1011C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

GRIN1 p.Arg337=

Q: What condition is associated with GRIN1 p.Arg337= (c.1011C>T)?

GRIN1 p.Arg337= (c.1011C>T) is associated with neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant (ClinVar).

c.1011C>T · rs138950430 · VCV1902397

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -2.3
Overall
CADD	0.229	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00062% 10/1,613,388 alleles · very rare exomes 9/1,461,304 · genomes 1/152,084 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
South Asian	0.0022%	45,542
Admixed American	0.00167%	59,984
African / African-American	0.00134%	74,888
European (non-Finnish)	0.000424%	235,995

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.Arg337=
Coding: c.1011C>T
MANE Select: NM_007327
dbSNP: rs138950430
Type: single nucleotide variant
Location: chr9:137158421 (GRCh38)
Structure: AlphaFold pLDDT 44.02
Residue 337: the 'disordered' region; a UniProt-annotated variant site (in)

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.Arg337His Likely benign ★ same residue
GPRIN1 p.Gly337Arg 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
GRIN1 p.Asp227His 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-arg337 (accessed [today's date]).

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