Is P2RX2 p.Ser351= (c.1053C>T) pathogenic?

P2RX2 p.Ser351= (c.1053C>T) is classified Likely benign in P2RX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-24). Ultra-rare (popmax 0.0512%, mid).

How common is P2RX2 p.Ser351= (c.1053C>T) in the general population?

P2RX2 p.Ser351= (c.1053C>T) is ultra-rare (popmax 0.0512%, mid) (gnomAD).

P2RX2 p.Ser351=

c.1053C>T · rs763073673 · VCV1900956

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, mid)

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 1.4	phastCons 1
Overall
CADD	14.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0512% Middle Eastern · 3/5,864 alleles

Filtering AF 0.0139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00742%

Overall 0.000955% 15/1,571,126 alleles · ultra-rare exomes 10/1,418,944 · genomes 5/152,182 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0512%	1,955
African / African-American	0.00678%	14,752
Remaining individualsnot grpmax-eligible	0.00165%	60,484
South Asian	0.00118%	84,492
European (non-Finnish)	0.000432%	231,375

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.Ser351=
Coding: c.1053C>T
MANE Select: NM_170682
dbSNP: rs763073673
Type: single nucleotide variant
Location: chr12:132621531 (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.Ser351Ala 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
P2RX2 p.Arg324Cys 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-ser351 (accessed [today's date]).

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