Is GRIN2D p.Arg1237Trp (c.3709C>T) pathogenic?

GRIN2D p.Arg1237Trp (c.3709C>T) is classified Uncertain significance in GRIN2D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-06). AlphaMissense: likely benign (0.2195); Very rare (popmax 0.000107%); Associated with Inborn genetic diseases.

What condition is associated with GRIN2D p.Arg1237Trp (c.3709C>T)?

GRIN2D p.Arg1237Trp (c.3709C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRIN2D p.Arg1237Trp (c.3709C>T) in the general population?

GRIN2D p.Arg1237Trp (c.3709C>T) is very rare (popmax 0.000107%) (gnomAD).

What do computational predictors say about GRIN2D p.Arg1237Trp (c.3709C>T)?

AlphaMissense predicts likely benign (score 0.2195) — an in-silico prediction, not a clinical call.

GRIN2D p.Arg1237Trp

c.3709C>T · rs1971337796 · VCV2775662

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2195 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000107%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2195	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -8.28	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 4.5	GERP 0.76, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 1,409 bp · p 0.013 · regional, not allelic
Overall
CADD	19.46	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 0.000107%

Overall 0.000107% 1/935,420 alleles · very rare

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.Arg1237Trp
Coding: c.3709C>T
MANE Select: NM_000836
dbSNP: rs1971337796
Type: single nucleotide variant
Location: chr19:48443635 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.00 · 13 PDB
Residue 1237: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRIN2D p.Arg1237Gln Uncertain significance ★ ⚠ same residue
GRIN2D p.Ala1032Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1135Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1208Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1244Val Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1256Thr Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala1310Gly Uncertain significance ★★ ⚠ same condition
GRIN2D p.Ala149Val Uncertain significance ★★ ⚠ 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/grin2d-p-arg1237trp (accessed [today's date]).

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