Is P2RY12 p.Phe182= (c.546C>T) pathogenic?

P2RY12 p.Phe182= (c.546C>T) is classified Benign in P2RY12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele.

P2RY12 p.Phe182=

Q: How common is P2RY12 p.Phe182= (c.546C>T) in the general population?

P2RY12 p.Phe182= (c.546C>T) is common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.546C>T · rs16863320 · VCV2115234

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -5.3, phastCons 0.15
Overall
CADD	8.507	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.8% African / African-American · 9,573/74,952 alleles

Filtering AF 12.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.5%

Overall 0.67% 10,817/1,613,960 alleles · common exomes 5,492/1,461,800 · genomes 5,325/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.8%	8
Remaining individualsnot grpmax-eligible	0.891%	112
Admixed American	0.765%	131
Middle Eastern	0.429%	233
South Asian	0.0439%	2,277
European (non-Finnish)	0.0135%	7,421
East Asian	0.00446%	22,432
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Phe182=
Coding: c.546C>T
MANE Select: NM_022788
dbSNP: rs16863320
Type: single nucleotide variant
Location: chr3:151338300 (GRCh38)
Gene constraint: LOEUF 1.16 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 85.11 · 5 PDB
Residue 182: an α-helix

Full P2RY12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MED12L p.Arg1245Ter Pathogenic/Likely pathogenic ★★ same type
P2RY12 p.Arg265Pro Pathogenic/Likely pathogenic ★★ ⚠ same type
P2RY12 p.Arg265Trp Uncertain significance ★★ ⚠ same type
P2RY12 p.Leu40Phe Uncertain significance ★★ ⚠ same type
MED12L p.Thr1183Met Likely benign ★★ same type
MED12L p.Asn1096Asp Uncertain significance ★ ⚠ same type
MED12L p.Glu1276Asp Uncertain significance ★ ⚠ same type
P2RY12 p.Arg122His Conflicting classifications of pathogenicity ★ ⚠ 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/p2ry12-p-phe182 (accessed [today's date]).

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