Is P2RX2 p.Val352Ile (c.1054G>A) pathogenic?

P2RX2 p.Val352Ile (c.1054G>A) is classified Conflicting classifications of pathogenicity in P2RX2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-01). AlphaMissense: likely benign (0.0623); Ultra-rare (popmax 0.0909%, sas).

How common is P2RX2 p.Val352Ile (c.1054G>A) in the general population?

P2RX2 p.Val352Ile (c.1054G>A) is ultra-rare (popmax 0.0909%, sas) (gnomAD).

What do computational predictors say about P2RX2 p.Val352Ile (c.1054G>A)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

P2RX2 p.Val352Ile

c.1054G>A · rs775460016 · VCV733323

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0909%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,152 bp · p 0.32 · regional, not allelic
Overall
CADD	12.53	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0909% South Asian · 77/84,738 alleles

Filtering AF 0.0745% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0685%

Overall 0.00884% 139/1,571,966 alleles · ultra-rare exomes 131/1,419,812 · genomes 8/152,154 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0909%	1,100
Remaining individualsnot grpmax-eligible	0.0149%	6,723
Admixed American	0.0072%	13,898
African / African-American	0.00407%	24,579
European (non-Finnish)	0.00397%	25,159

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.Val352Ile
Coding: c.1054G>A
MANE Select: NM_170682
dbSNP: rs775460016
Type: single nucleotide variant
Location: chr12:132621532 (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.Val352= Likely benign ★ 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-val352ile (accessed [today's date]).

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