Is GPER1 p.Arg286Pro (c.857G>C) pathogenic?

GPER1 p.Arg286Pro (c.857G>C) is classified Uncertain significance in GPER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: likely benign (0.0947); Very rare (popmax 0.00102%, nfe).

How common is GPER1 p.Arg286Pro (c.857G>C) in the general population?

GPER1 p.Arg286Pro (c.857G>C) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about GPER1 p.Arg286Pro (c.857G>C)?

AlphaMissense predicts likely benign (score 0.0947) — an in-silico prediction, not a clinical call.

GPER1 p.Arg286Pro

c.857G>C · VCV4031250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0947 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0947	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.8	GERP -4.2, phastCons 0.95
Regional constraint	o/e 0.82	unconstrained · MANE · 1,124 bp · p 4.7e-05 · regional, not allelic
Overall
CADD	9.861	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 0.00102% European (non-Finnish) · 12/1,180,034 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000745% 12/1,611,134 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: GPER1
Protein: p.Arg286Pro
Coding: c.857G>C
MANE Select: NM_001318252 · reported on NM_001098201
Type: single nucleotide variant
Location: chr7:1092585 (GRCh38)

Full GPER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/gper1-p-arg286pro (accessed [today's date]).

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