Is P2RX2 p.Val352= (c.1056C>T) pathogenic?

P2RX2 p.Val352= (c.1056C>T) is classified Likely benign in P2RX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). Ultra-rare (popmax 0.0108%, amr).

How common is P2RX2 p.Val352= (c.1056C>T) in the general population?

P2RX2 p.Val352= (c.1056C>T) is ultra-rare (popmax 0.0108%, amr) (gnomAD).

P2RX2 p.Val352=

c.1056C>T · rs751840679 · VCV1649702

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, amr)

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 -11
Overall
CADD	3.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0108% Admixed American · 6/55,696 alleles

Filtering AF 0.00466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00313%

Overall 0.00172% 27/1,572,996 alleles · ultra-rare exomes 27/1,420,728 · genomes 0/152,268 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0108%	9,283
European (non-Finnish)	0.00164%	60,934
African / African-American	0.00135%	73,876
South Asian	0.00118%	84,998

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.Val352=
Coding: c.1056C>T
MANE Select: NM_170682
dbSNP: rs751840679
Type: single nucleotide variant
Location: chr12:132621534 (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.Val352Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
P2RX2 p.Val352Gly 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-val352 (accessed [today's date]).

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