Is P2RX2 p.Ala3= (c.9C>T) pathogenic?

P2RX2 p.Ala3= (c.9C>T) is classified Benign in P2RX2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-25). Common (popmax 7.95%, afr) — too common for a highly-penetrant pathogenic allele.

P2RX2 p.Ala3=

Q: How common is P2RX2 p.Ala3= (c.9C>T) in the general population?

P2RX2 p.Ala3= (c.9C>T) is common (popmax 7.95%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9C>T · rs186684886 · VCV226991

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 7.95%, 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.
REVEL	0.011	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.5	GERP -3.6
Overall
CADD	4.394	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.95% African / African-American · 5,165/64,974 alleles

Filtering AF 7.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.69%

Overall 0.458% 5,875/1,283,212 alleles · common exomes 2,419/1,132,454 · genomes 3,456/150,758 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.95%	13
Admixed American	0.8%	125
Middle Eastern	0.752%	133
Remaining individualsnot grpmax-eligible	0.571%	175
European (non-Finnish)	0.021%	4,762
South Asian	0.0111%	8,976

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: P2RX2
Protein: p.Ala3=
Coding: c.9C>T
MANE Select: NM_170682
dbSNP: rs186684886
Type: single nucleotide variant
Location: chr12:132618825 (GRCh38)
Gene constraint: LOEUF 1.276 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.80 · 18 PDB

Full P2RX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

P2RX2 p.Ala3Ser Uncertain significance ★ ⚠ same residue
P2RX2 p.Ala3fs Uncertain significance ★ same residue
P2RX2 c.174-1G>A Uncertain significance ★★ same type
P2RX2 p.Arg218His Uncertain significance ★★ ⚠ same type
P2RX2 p.Arg286Gln Uncertain significance ★★ ⚠ same type
P2RX2 p.Arg302Thr Uncertain significance ★★ ⚠ same type
P2RX2 p.Arg315Cys Uncertain significance ★★ ⚠ same type
P2RX2 p.Arg315His 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/p2rx2-p-ala3 (accessed [today's date]).

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