Is GRIN2D p.Arg313Trp (c.937C>T) pathogenic?

GRIN2D p.Arg313Trp (c.937C>T) is classified Uncertain significance in GRIN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). AlphaMissense: likely pathogenic (0.6725); Very rare (popmax 0.00935%, afr).

How common is GRIN2D p.Arg313Trp (c.937C>T) in the general population?

GRIN2D p.Arg313Trp (c.937C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about GRIN2D p.Arg313Trp (c.937C>T)?

AlphaMissense predicts likely pathogenic (score 0.6725) — an in-silico prediction, not a clinical call.

GRIN2D p.Arg313Trp

c.937C>T · rs373524397 · VCV1902333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6725 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6725	likely pathogenic
REVEL	0.198	benign-leaning
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.28	GERP -3.6, phastCons 0.97
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 5.9e-06 · regional, not allelic
Overall
CADD	22.8	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 0.00935% African / African-American · 7/74,850 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000562% 9/1,602,796 alleles · very rare exomes 6/1,450,578 · genomes 3/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,693
East Asian	0.00224%	44,712
European (non-Finnish)	8.49e-05%	1,178,169

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: GRIN2D
Protein: p.Arg313Trp
Coding: c.937C>T
MANE Select: NM_000836
dbSNP: rs373524397
Type: single nucleotide variant
Location: chr19:48405205 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.00 · 13 PDB

Full GRIN2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRIN2D p.Arg313Gln Uncertain significance ★ ⚠ same residue
GRIN2D p.Arg313= Likely benign ★ same residue
GRIN2D p.Met681Val Pathogenic/Likely pathogenic ★★ same type
GRIN2D p.Val667Ile Pathogenic/Likely pathogenic ★★ same type
GRIN2D p.Ala1032Val Uncertain significance ★★ ⚠ same type
GRIN2D p.Ala1040Thr Uncertain significance ★★ ⚠ same type
GRIN2D p.Ala1085Thr Uncertain significance ★★ ⚠ same type
GRIN2D p.Ala1135Thr 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/grin2d-p-arg313trp (accessed [today's date]).

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