Is GRIN2A p.Arg504Pro (c.1511G>C) pathogenic?

GRIN2A p.Arg504Pro (c.1511G>C) is classified Uncertain significance in GRIN2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-20). AlphaMissense: likely pathogenic (0.9935); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GRIN2A p.Arg504Pro (c.1511G>C)?

GRIN2A p.Arg504Pro (c.1511G>C) is associated with Inborn genetic diseases (ClinVar).

How common is GRIN2A p.Arg504Pro (c.1511G>C) in the general population?

GRIN2A p.Arg504Pro (c.1511G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRIN2A p.Arg504Pro (c.1511G>C)?

AlphaMissense predicts likely pathogenic (score 0.9935) — an in-silico prediction, not a clinical call.

GRIN2A p.Arg504Pro

c.1511G>C · rs1331671132 · VCV3102466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9935 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9935	likely pathogenic
REVEL	0.345	indeterminate
SaProt	LLR -16.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 12 kb · p 4.2e-21 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: GRIN2A
Protein: p.Arg504Pro
Coding: c.1511G>C
MANE Select: NM_001134407
dbSNP: rs1331671132
Type: single nucleotide variant
Location: chr16:9840787 (GRCh38)
Gene constraint: LOEUF 0.268 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 60.70 · 37 PDB
Residue 504: a UniProt-annotated variant site (found in schizophrenia; uncertain significance; loss of function in ion transmembrane transport; the channel is not activated by glutamate); a UniProt-annotated variant site (in fesd; decreased protein abundance; decreased localization to the cell membrane; no significant effect on calcium ion transmembrane import into cytosol)

Full GRIN2A 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

GRIN2A p.Arg504Gln Uncertain significance ★ ⚠ same residue
GRIN2A p.Arg504Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
GRIN2A p.Ala635Thr Pathogenic/Likely pathogenic ★★ same condition
GRIN2A p.Pro552Arg Pathogenic ★★ same condition
GRIN2A p.Ala108Val Uncertain significance ★★ ⚠ same condition
GRIN2A p.Ala604Gly Uncertain significance ★★ ⚠ same condition
GRIN2A p.Arg1417Gln Uncertain significance ★★ ⚠ same condition
GRIN2A p.Arg431Ser 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/grin2a-p-arg504pro (accessed [today's date]).

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