Is GPR132 p.Pro366Arg (c.1097C>G) pathogenic?

GPR132 p.Pro366Arg (c.1097C>G) is classified Uncertain significance in GPR132 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely benign (0.0781); Ultra-rare (popmax 0.0111%, eas).

How common is GPR132 p.Pro366Arg (c.1097C>G) in the general population?

GPR132 p.Pro366Arg (c.1097C>G) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about GPR132 p.Pro366Arg (c.1097C>G)?

AlphaMissense predicts likely benign (score 0.0781) — an in-silico prediction, not a clinical call.

GPR132 p.Pro366Arg

c.1097C>G · VCV4265681

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0781 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0781	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.91	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 0.94	GERP -1.5, phastCons 0.003
Regional constraint	o/e 0.79	unconstrained · MANE · 4,423 bp · p 1.7e-06 · regional, not allelic
Overall
CADD	7.201	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 0.0111% East Asian · 5/44,894 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000496% 8/1,613,962 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,979
Remaining individualsnot grpmax-eligible	0.0016%	62,472
African / African-American	0.00133%	74,930
European (non-Finnish)	8.47e-05%	1,179,948

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: GPR132
Protein: p.Pro366Arg
Coding: c.1097C>G
MANE Select: NM_013345
Type: single nucleotide variant
Location: chr14:105051040 (GRCh38)
Gene constraint: LOEUF 1.905 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 79.86 · 4 PDB

Full GPR132 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GPR132 p.Pro366Thr Uncertain significance ★ ⚠ same residue
GPR132 p.Ala352Ser Benign ★★ same type
GPR132 p.Leu169= Benign ★★ same type
GPR132 p.Ser243= Benign ★★ same type
GPR132 p.Ala159Thr Uncertain significance ★ ⚠ same type
GPR132 p.Ala164Ser Uncertain significance ★ ⚠ same type
GPR132 p.Ala164Thr Uncertain significance ★ ⚠ same type
GPR132 p.Ala256Pro 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/gpr132-p-pro366arg (accessed [today's date]).

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