Is GPR4 p.Ser295Arg (c.885C>G) pathogenic?

GPR4 p.Ser295Arg (c.885C>G) is classified Uncertain significance in GPR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.22); Absent from gnomAD v4.1.

How common is GPR4 p.Ser295Arg (c.885C>G) in the general population?

GPR4 p.Ser295Arg (c.885C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GPR4 p.Ser295Arg (c.885C>G)?

AlphaMissense predicts likely benign (score 0.22) — an in-silico prediction, not a clinical call.

GPR4 p.Ser295Arg

c.885C>G · VCV3522059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.22 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.22	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -2.73	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 -1.3	GERP -4
Regional constraint	o/e 0.87	unconstrained · MANE · 239 bp · p 0.17 · regional, not allelic
Overall
CADD	0.377	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: GPR4
Protein: p.Ser295Arg
Coding: c.885C>G
MANE Select: NM_005282
Type: single nucleotide variant
Location: chr19:45590982 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.97 · 25 PDB
Residue 295: a UniProt-annotated variant site (in); 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.Arg263Cys Uncertain significance ★ ⚠ same type
GPR4 p.Arg306Cys 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-ser295arg (accessed [today's date]).

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