Is P2RY12 p.Phe246= (c.738T>C) pathogenic?

P2RY12 p.Phe246= (c.738T>C) is classified Likely benign in P2RY12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-18). Ultra-rare (popmax 0.0784%, amr).

How common is P2RY12 p.Phe246= (c.738T>C) in the general population?

P2RY12 p.Phe246= (c.738T>C) is ultra-rare (popmax 0.0784%, amr) (gnomAD).

P2RY12 p.Phe246=

c.738T>C · rs186893035 · VCV2168742

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0784%, 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 -1.6	GERP -5.6
Overall
CADD	2.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0784% Admixed American · 47/59,970 alleles

Filtering AF 0.0605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.0129% 208/1,614,056 alleles · ultra-rare exomes 169/1,461,726 · genomes 39/152,330 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0784%	1,276
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.0126%	7,919
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
African / African-American	0.00267%	37,516

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.Phe246=
Coding: c.738T>C
MANE Select: NM_022788
dbSNP: rs186893035
Type: single nucleotide variant
Location: chr3:151338108 (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-phe246 (accessed [today's date]).

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