Is GPR4 p.Arg263Cys (c.787C>T) pathogenic?

GPR4 p.Arg263Cys (c.787C>T) is classified Uncertain significance in GPR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-21). AlphaMissense: likely benign (0.3165); Very rare (popmax 0.00653%, nfe).

How common is GPR4 p.Arg263Cys (c.787C>T) in the general population?

GPR4 p.Arg263Cys (c.787C>T) is very rare (popmax 0.00653%, nfe) (gnomAD).

What do computational predictors say about GPR4 p.Arg263Cys (c.787C>T)?

AlphaMissense predicts likely benign (score 0.3165) — an in-silico prediction, not a clinical call.

GPR4 p.Arg263Cys

c.787C>T · rs753280506 · VCV2508727

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3165 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00653%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3165	likely benign
REVEL	0.489	indeterminate
SaProt	LLR -11.76	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 0.91, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 805 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.00653% European (non-Finnish) · 77/1,180,030 alleles

Filtering AF 0.0053% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0049%

Overall 0.00514% 83/1,613,742 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00653%	15,325
African / African-American	0.00534%	18,736
Remaining individualsnot grpmax-eligible	0.0016%	62,480
South Asian	0.0011%	91,094

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: GPR4
Protein: p.Arg263Cys
Coding: c.787C>T
MANE Select: NM_005282
dbSNP: rs753280506
Type: single nucleotide variant
Location: chr19:45591080 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.97 · 25 PDB
Residue 263: an α-helix

Full GPR4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPR4 p.Ala195Thr Uncertain significance ★ ⚠ same type
GPR4 p.Ala195Val Uncertain significance ★ ⚠ same type
GPR4 p.Ala231Val Uncertain significance ★ ⚠ same type
GPR4 p.Ala293Thr Uncertain significance ★ ⚠ same type
GPR4 p.Arg216Leu Uncertain significance ★ ⚠ same type
GPR4 p.Arg254His Uncertain significance ★ ⚠ same type
GPR4 p.Arg306Cys Uncertain significance ★ ⚠ same type
GPR4 p.Arg44Cys 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/gpr4-p-arg263cys (accessed [today's date]).

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