Is P2RY2 p.Pro293Leu (c.878C>T) pathogenic?

P2RY2 p.Pro293Leu (c.878C>T) is classified Uncertain significance in P2RY2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely pathogenic (0.9169); Very rare (popmax 0.00229%, nfe).

How common is P2RY2 p.Pro293Leu (c.878C>T) in the general population?

P2RY2 p.Pro293Leu (c.878C>T) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about P2RY2 p.Pro293Leu (c.878C>T)?

AlphaMissense predicts likely pathogenic (score 0.9169) — an in-silico prediction, not a clinical call.

P2RY2 p.Pro293Leu

c.878C>T · rs773254428 · VCV2321761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9169 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9169	likely pathogenic
REVEL	0.397	indeterminate
SaProt	LLR -17.45	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP -0.14, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 1,130 bp · p 0.024 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00229% European (non-Finnish) · 27/1,179,950 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00187% 30/1,608,138 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,702
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,444
African / African-American	0.00133%	74,922

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: P2RY2
Protein: p.Pro293Leu
Coding: c.878C>T
MANE Select: NM_002564
dbSNP: rs773254428
Type: single nucleotide variant
Location: chr11:73235037 (GRCh38)
Gene constraint: LOEUF 1.917 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 79.11 · 3 PDB
Residue 293: an α-helix

Full P2RY2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

P2RY2 p.Ala176Thr Uncertain significance ★ ⚠ same type
P2RY2 p.Ala252Thr Uncertain significance ★ ⚠ same type
P2RY2 p.Ala287Val Uncertain significance ★ ⚠ same type
P2RY2 p.Ala309Pro Uncertain significance ★ ⚠ same type
P2RY2 p.Ala80Thr Uncertain significance ★ ⚠ same type
P2RY2 p.Ala94Asp Uncertain significance ★ ⚠ same type
P2RY2 p.Ala94Val Uncertain significance ★ ⚠ same type
P2RY2 p.Arg143Cys 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/p2ry2-p-pro293leu (accessed [today's date]).

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