Is P2RY12 p.Phe59= (c.177T>C) pathogenic?

P2RY12 p.Phe59= (c.177T>C) is classified Likely benign in P2RY12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-26). Very rare (popmax 0.00167%, amr).

How common is P2RY12 p.Phe59= (c.177T>C) in the general population?

P2RY12 p.Phe59= (c.177T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

P2RY12 p.Phe59=

c.177T>C · rs1252629428 · VCV2888459

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

⚠ 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 -0.059	GERP -5.3, phastCons 0.27
Overall
CADD	6.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,892 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000496% 8/1,613,778 alleles · very rare exomes 6/1,461,618 · genomes 2/152,160 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,892
South Asian	0.0011%	91,072
European (non-Finnish)	0.000508%	196,661

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: P2RY12
Protein: p.Phe59=
Coding: c.177T>C
MANE Select: NM_022788
dbSNP: rs1252629428
Type: single nucleotide variant
Location: chr3:151338669 (GRCh38)

Full P2RY12 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/p2ry12-p-phe59 (accessed [today's date]).

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