Is GRPR p.His380= (c.1140C>T) pathogenic?

GRPR p.His380= (c.1140C>T) is classified Likely benign in GRPR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Ultra-rare (popmax 0.0457%, mid).

How common is GRPR p.His380= (c.1140C>T) in the general population?

GRPR p.His380= (c.1140C>T) is ultra-rare (popmax 0.0457%, mid) (gnomAD).

GRPR p.His380=

c.1140C>T · rs773791112 · VCV2660063

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0457%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -3.3
Overall
CADD	0.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0457% Middle Eastern · 2/4,373 alleles

Filtering AF 0.0191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00919% 111/1,207,330 alleles · ultra-rare exomes 108/1,096,346 · genomes 3/110,984 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0457%	2,186
South Asian	0.03%	3,335
European (non-Finnish)	0.00963%	10,389
Remaining individualsnot grpmax-eligible	0.00631%	15,850
Admixed American	0.00438%	22,825
African / African-American	0.00176%	56,803

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.His380=
Coding: c.1140C>T
MANE Select: NM_005314
dbSNP: rs773791112
Type: single nucleotide variant
Location: chrX:16152630 (GRCh38)
Structure: AlphaFold pLDDT 78.78 · 4 PDB

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.Arg261Gln Uncertain significance ★ ⚠ same type
GRPR p.Arg287Leu 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-his380 (accessed [today's date]).

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