Is GRIN2D p.Arg735Pro (c.2204G>C) pathogenic?

GRIN2D p.Arg735Pro (c.2204G>C) is classified Uncertain significance in GRIN2D (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely pathogenic (0.6653); Absent from gnomAD v4.1.

How common is GRIN2D p.Arg735Pro (c.2204G>C) in the general population?

GRIN2D p.Arg735Pro (c.2204G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIN2D p.Arg735Pro (c.2204G>C)?

AlphaMissense predicts likely pathogenic (score 0.6653) — an in-silico prediction, not a clinical call.

GRIN2D p.Arg735Pro

c.2204G>C · rs749130026 · VCV1708819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6653 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6653	likely pathogenic
REVEL	0.275	benign-leaning
SaProt	LLR -13.76	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.53	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.4	GERP 0.41, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 23 kb · p 8.9e-16 · regional, not allelic
Overall
CADD	33.0	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

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.Arg735Pro
Coding: c.2204G>C
MANE Select: NM_000836
dbSNP: rs749130026
Type: single nucleotide variant
Location: chr19:48421897 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.00 · 13 PDB
Residue 735: a β-strand

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

Similar variants

GRIN2D p.Arg735Leu 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
GRIN2D p.Ala1177Thr 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-arg735pro (accessed [today's date]).

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