Is GPER1 p.Pro36Arg (c.107C>G) pathogenic?

GPER1 p.Pro36Arg (c.107C>G) is classified Uncertain significance in GPER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely benign (0.0665); Very rare (popmax 0.00224%, eas).

How common is GPER1 p.Pro36Arg (c.107C>G) in the general population?

GPER1 p.Pro36Arg (c.107C>G) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about GPER1 p.Pro36Arg (c.107C>G)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

GPER1 p.Pro36Arg

c.107C>G · VCV3854980

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.4	GERP -4
Regional constraint	o/e 0.82	unconstrained · MANE · 1,124 bp · p 4.7e-05 · regional, not allelic
Overall
CADD	0.024	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 0.00224% East Asian · 1/44,718 alleles

Overall 0.000124% 2/1,607,848 alleles · very rare exomes 2/1,455,488 · genomes 0/152,360 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,718
European (non-Finnish)	8.51e-05%	1,175,315

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.Pro36Arg
Coding: c.107C>G
MANE Select: NM_001098201
Type: single nucleotide variant
Location: chr7:1091835 (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-pro36arg (accessed [today's date]).

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