Is GPR3 p.Pro26Ser (c.76C>T) pathogenic?

GPR3 p.Pro26Ser (c.76C>T) is classified Likely benign in GPR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). AlphaMissense: likely benign (0.077); Absent from gnomAD v4.1.

How common is GPR3 p.Pro26Ser (c.76C>T) in the general population?

GPR3 p.Pro26Ser (c.76C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GPR3 p.Pro26Ser (c.76C>T)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

GPR3 p.Pro26Ser

c.76C>T · VCV3522008

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.54	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 3.3	GERP 0.076, phastCons 0.98
Regional constraint	o/e 0.76	unconstrained · MANE · 989 bp · p 8.9e-07 · regional, not allelic
Overall
CADD	11.99	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: GPR3
Protein: p.Pro26Ser
Coding: c.76C>T
MANE Select: NM_005281
Type: single nucleotide variant
Location: chr1:27393874 (GRCh38)
Gene constraint: LOEUF 1.405 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.13 · 8 PDB

Full GPR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPR3 p.Ala106Val Uncertain significance ★ ⚠ same type
GPR3 p.Ala10Ser Uncertain significance ★ ⚠ same type
GPR3 p.Ala236Ser Uncertain significance ★ ⚠ same type
GPR3 p.Ala35Thr Uncertain significance ★ ⚠ same type
GPR3 p.Ala42Val Uncertain significance ★ ⚠ same type
GPR3 p.Arg134Cys Uncertain significance ★ ⚠ same type
GPR3 p.Arg152Gln Uncertain significance ★ ⚠ same type
GPR3 p.Arg152Trp 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/gpr3-p-pro26ser (accessed [today's date]).

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