Is GRIN2D p.Arg478Pro (c.1433G>C) pathogenic?

GRIN2D p.Arg478Pro (c.1433G>C) is classified Uncertain significance in GRIN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: likely benign (0.1442); Absent from gnomAD v4.1.

How common is GRIN2D p.Arg478Pro (c.1433G>C) in the general population?

GRIN2D p.Arg478Pro (c.1433G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIN2D p.Arg478Pro (c.1433G>C)?

AlphaMissense predicts likely benign (score 0.1442) — an in-silico prediction, not a clinical call.

GRIN2D p.Arg478Pro

c.1433G>C · rs2513671733 · VCV2695153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1442 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1442	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -4.59	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 11	GERP 0.53, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 5,266 bp · p 6.3e-14 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRIN2D
Protein: p.Arg478Pro
Coding: c.1433G>C
MANE Select: NM_000836
dbSNP: rs2513671733
Type: single nucleotide variant
Location: chr19:48414884 (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.Arg478= Conflicting classifications of pathogenicity ★ same residue
GRIN2D p.Arg478Gly Uncertain significance ★ ⚠ 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-arg478pro (accessed [today's date]).

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