Is GRPR p.Arg261Gln (c.782G>A) pathogenic?

GRPR p.Arg261Gln (c.782G>A) is classified Uncertain significance in GRPR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-23). AlphaMissense: likely benign (0.2205); Very rare (popmax 0.00219%, amr).

How common is GRPR p.Arg261Gln (c.782G>A) in the general population?

GRPR p.Arg261Gln (c.782G>A) is very rare (popmax 0.00219%, amr) (gnomAD).

What do computational predictors say about GRPR p.Arg261Gln (c.782G>A)?

AlphaMissense predicts likely benign (score 0.2205) — an in-silico prediction, not a clinical call.

GRPR p.Arg261Gln

c.782G>A · VCV3522935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2205	likely benign
REVEL	0.448	indeterminate
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 2,064 bp · p 0.39 · regional, not allelic
Overall
CADD	28.9	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 0.00219% Admixed American · 1/45,660 alleles

Filtering AF 0.000326% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00021%

Overall 0.000664% 8/1,205,653 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00219%	45,660
European (non-Finnish)	0.000785%	127,416

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: GRPR
Protein: p.Arg261Gln
Coding: c.782G>A
MANE Select: NM_005314
Type: single nucleotide variant
Location: chrX:16152272 (GRCh38)
Structure: AlphaFold pLDDT 78.78 · 4 PDB
Residue 261: an α-helix

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

Similar variants

GRPR p.Lys362= Likely benign ★★ same type
GRPR p.Thr132= Benign ★★ same type
GRPR p.Val220Ile Likely benign ★★ same type
GRPR p.Ala136Val Uncertain significance ★ ⚠ same type
GRPR p.Ala369Val Uncertain significance ★ ⚠ same type
GRPR p.Arg144Trp Uncertain significance ★ ⚠ same type
GRPR p.Arg287Leu Uncertain significance ★ ⚠ same type
GRPR p.Arg347Gln 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/grpr-p-arg261gln (accessed [today's date]).

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