Is GRPR p.Ser363Arg (c.1089T>G) pathogenic?

GRPR p.Ser363Arg (c.1089T>G) is classified Uncertain significance in GRPR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: ambiguous (0.3402); Absent from gnomAD v4.1.

How common is GRPR p.Ser363Arg (c.1089T>G) in the general population?

GRPR p.Ser363Arg (c.1089T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRPR p.Ser363Arg (c.1089T>G)?

AlphaMissense predicts ambiguous (score 0.3402) — an in-silico prediction, not a clinical call.

GRPR p.Ser363Arg

c.1089T>G · VCV3522931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3402 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3402	ambiguous
REVEL	0.23	benign-leaning
SaProt	LLR -6.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -3.3
Regional constraint	o/e 1.08	unconstrained · MANE · 2,064 bp · p 0.39 · regional, not allelic
Overall
CADD	6.878	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GRPR
Protein: p.Ser363Arg
Coding: c.1089T>G
MANE Select: NM_005314
Type: single nucleotide variant
Location: chrX:16152579 (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-ser363arg (accessed [today's date]).

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