Is GRIN2A p.Asp1237Val (c.3710A>T) pathogenic?

GRIN2A p.Asp1237Val (c.3710A>T) is classified Uncertain significance in GRIN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-30). AlphaMissense: ambiguous (0.362); Very rare (popmax 8.47e-05%, nfe).

How common is GRIN2A p.Asp1237Val (c.3710A>T) in the general population?

GRIN2A p.Asp1237Val (c.3710A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about GRIN2A p.Asp1237Val (c.3710A>T)?

AlphaMissense predicts ambiguous (score 0.362) — an in-silico prediction, not a clinical call.

GRIN2A p.Asp1237Val

c.3710A>T · VCV3766001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.362 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.362	ambiguous
REVEL	0.471	indeterminate
SaProt	LLR -7.54	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 5,758 bp · p 0.13 · regional, not allelic
Overall
CADD	25.7	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 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 6.2e-05% 1/1,614,104 alleles · very rare exomes 1/1,461,874 · genomes 0/152,230 · 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: GRIN2A
Protein: p.Asp1237Val
Coding: c.3710A>T
MANE Select: NM_001134407
Type: single nucleotide variant
Location: chr16:9763834 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 37 PDB
Residue 1237: a UniProt-annotated variant site (found in schizophrenia; uncertain significance; loss of function in ion transmembrane transport; the channel is not activated by glutamate)

Full GRIN2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRIN2A p.Asp1237Glu Uncertain significance ★ ⚠ same residue
GRIN2A c.1007+1G>A Pathogenic/Likely pathogenic ★★ same type
GRIN2A c.1007+1G>T Pathogenic ★★ same type
GRIN2A c.1123-2A>G Pathogenic/Likely pathogenic ★★ same type
GRIN2A c.1497+1G>T Pathogenic/Likely pathogenic ★★ same type
GRIN2A c.2007+1G>T Likely pathogenic ★★ same type
GRIN2A c.2168+1G>C Pathogenic/Likely pathogenic ★★ same type
GRIN2A c.415-2A>G Likely pathogenic ★★ 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/grin2a-p-asp1237val (accessed [today's date]).

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