Is GRIN2D p.Arg798Pro (c.2393G>C) pathogenic?

GRIN2D p.Arg798Pro (c.2393G>C) is classified Uncertain significance in GRIN2D (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-08-28). AlphaMissense: likely benign (0.2689); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GRIN2D p.Arg798Pro (c.2393G>C)?

GRIN2D p.Arg798Pro (c.2393G>C) is associated with Inborn genetic diseases (ClinVar).

How common is GRIN2D p.Arg798Pro (c.2393G>C) in the general population?

GRIN2D p.Arg798Pro (c.2393G>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about GRIN2D p.Arg798Pro (c.2393G>C)?

AlphaMissense predicts likely benign (score 0.2689) — an in-silico prediction, not a clinical call.

GRIN2D p.Arg798Pro

c.2393G>C · rs371691127 · VCV2316350

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2689 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2689	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -8.12	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 6.5	GERP 1.4, 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

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 0.00017% European (non-Finnish) · 2/1,179,724 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,459,604 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.Arg798Pro
Coding: c.2393G>C
MANE Select: NM_000836
dbSNP: rs371691127
Type: single nucleotide variant
Location: chr19:48441909 (GRCh38)
Gene constraint: LOEUF 0.642 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.00 · 13 PDB
Residue 798: a disulfide bond

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.Arg798Gly Uncertain significance ★ ⚠ same residue
GRIN2D p.Arg798His 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-arg798pro (accessed [today's date]).

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