Is GRIN2D p.Arg1237Gln (c.3710G>A) pathogenic?

GRIN2D p.Arg1237Gln (c.3710G>A) is classified Uncertain significance in GRIN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-20). AlphaMissense: likely benign (0.144); Very rare (popmax 0.000223%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GRIN2D p.Arg1237Gln (c.3710G>A)?

GRIN2D p.Arg1237Gln (c.3710G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GRIN2D p.Arg1237Gln (c.3710G>A) in the general population?

GRIN2D p.Arg1237Gln (c.3710G>A) is very rare (popmax 0.000223%, nfe) (gnomAD).

What do computational predictors say about GRIN2D p.Arg1237Gln (c.3710G>A)?

AlphaMissense predicts likely benign (score 0.144) — an in-silico prediction, not a clinical call.

GRIN2D p.Arg1237Gln

c.3710G>A · rs1473583586 · VCV986075

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.144 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000223%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.144	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.4	GERP 0.76, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 1,409 bp · p 0.013 · regional, not allelic
Overall
CADD	17.85	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 0.000223% European (non-Finnish) · 2/898,356 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000185% 2/1,083,354 alleles · very rare exomes 1/937,990 · genomes 1/145,364 · 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: GRIN2D
Protein: p.Arg1237Gln
Coding: c.3710G>A
MANE Select: NM_000836
dbSNP: rs1473583586
Type: single nucleotide variant
Location: chr19:48443636 (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.Arg1237Trp 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-arg1237gln (accessed [today's date]).

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