Is GPR22 p.Asp418= (c.1254T>C) pathogenic?

GPR22 p.Asp418= (c.1254T>C) is classified Likely benign in GPR22 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). Very rare (popmax 0.00823%, nfe).

How common is GPR22 p.Asp418= (c.1254T>C) in the general population?

GPR22 p.Asp418= (c.1254T>C) is very rare (popmax 0.00823%, nfe) (gnomAD).

GPR22 p.Asp418=

c.1254T>C · VCV3771507

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00823%, nfe)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.1	GERP -3.9
Overall
CADD	0.639	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00823% European (non-Finnish) · 96/1,165,930 alleles

Filtering AF 0.00689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0064%

Overall 0.00615% 97/1,576,598 alleles · very rare exomes 95/1,424,642 · genomes 2/151,956 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00823%	12,145
Remaining individualsnot grpmax-eligible	0.00165%	60,728

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: GPR22
Protein: p.Asp418=
Coding: c.1254T>C
MANE Select: NM_005295
Type: single nucleotide variant
Location: chr7:107475314 (GRCh38)

Full GPR22 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/gpr22-p-asp418 (accessed [today's date]).

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