Is P2RY14 p.Val91Glu (c.272T>A) pathogenic?

P2RY14 p.Val91Glu (c.272T>A) is classified Uncertain significance in P2RY14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: ambiguous (0.3626); Very rare (popmax 0.00439%, sas).

How common is P2RY14 p.Val91Glu (c.272T>A) in the general population?

P2RY14 p.Val91Glu (c.272T>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about P2RY14 p.Val91Glu (c.272T>A)?

AlphaMissense predicts ambiguous (score 0.3626) — an in-silico prediction, not a clinical call.

P2RY14 p.Val91Glu

c.272T>A · VCV4129769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3626 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3626	ambiguous
REVEL	0.234	benign-leaning
SaProt	LLR -10.47	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 1,013 bp · p 0.27 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.00439% South Asian · 4/91,082 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,614,164 alleles · very rare exomes 4/1,461,850 · genomes 0/152,314 · joint denominator

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: P2RY14
Protein: p.Val91Glu
Coding: c.272T>A
MANE Select: NM_014879
Type: single nucleotide variant
Location: chr3:151214045 (GRCh38)

Full P2RY14 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/p2ry14-p-val91glu (accessed [today's date]).

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