Is P2RY14 p.Ser4Pro (c.10T>C) pathogenic?

P2RY14 p.Ser4Pro (c.10T>C) is classified Uncertain significance in P2RY14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.1082); Very rare (popmax 8.48e-05%, nfe).

How common is P2RY14 p.Ser4Pro (c.10T>C) in the general population?

P2RY14 p.Ser4Pro (c.10T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about P2RY14 p.Ser4Pro (c.10T>C)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

P2RY14 p.Ser4Pro

c.10T>C · VCV3303813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -9.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.6	GERP -0.57, phastCons 0.001
Regional constraint	o/e 0.94	unconstrained · MANE · 1,013 bp · p 0.27 · regional, not allelic
Overall
CADD	15.84	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 8.48e-05% European (non-Finnish) · 1/1,179,232 alleles

Overall 6.2e-05% 1/1,612,640 alleles · very rare exomes 1/1,460,394 · genomes 0/152,246 · 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.Ser4Pro
Coding: c.10T>C
MANE Select: NM_014879
Type: single nucleotide variant
Location: chr3:151214307 (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-ser4pro (accessed [today's date]).

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