Is GRIN2D p.Pro952Arg (c.2855C>G) pathogenic?

GRIN2D p.Pro952Arg (c.2855C>G) is classified Uncertain significance in GRIN2D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-17). AlphaMissense: likely benign (0.0806); Ultra-rare (popmax 0.0768%, eas); Associated with Inborn genetic diseases.

What condition is associated with GRIN2D p.Pro952Arg (c.2855C>G)?

GRIN2D p.Pro952Arg (c.2855C>G) is associated with Inborn genetic diseases (ClinVar).

How common is GRIN2D p.Pro952Arg (c.2855C>G) in the general population?

GRIN2D p.Pro952Arg (c.2855C>G) is ultra-rare (popmax 0.0768%, eas) (gnomAD).

What do computational predictors say about GRIN2D p.Pro952Arg (c.2855C>G)?

AlphaMissense predicts likely benign (score 0.0806) — an in-silico prediction, not a clinical call.

GRIN2D p.Pro952Arg

c.2855C>G · VCV3616147

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0806 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0768%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0806	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -6.61	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 2	GERP 1, phastCons 0.039
Regional constraint	o/e 1.10	unconstrained · MANE · 1,409 bp · p 0.013 · regional, not allelic
Overall
CADD	15.75	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 0.0768% East Asian · 11/14,314 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0333%

Overall 0.00103% 11/1,068,224 alleles · ultra-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.Pro952Arg
Coding: c.2855C>G
MANE Select: NM_000836
Type: single nucleotide variant
Location: chr19:48442781 (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

Disease context

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

Similar variants

GRIN2D p.Pro952= Likely benign ★★ same residue
GRIN2D p.Pro952Leu 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

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-pro952arg (accessed [today's date]).

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