Is P2RX2 p.Arg16Pro (c.47G>C) pathogenic?

P2RX2 p.Arg16Pro (c.47G>C) is classified Uncertain significance in P2RX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-07). AlphaMissense: likely benign (0.1232); Ultra-rare (popmax 0.0205%, mid).

How common is P2RX2 p.Arg16Pro (c.47G>C) in the general population?

P2RX2 p.Arg16Pro (c.47G>C) is ultra-rare (popmax 0.0205%, mid) (gnomAD).

What do computational predictors say about P2RX2 p.Arg16Pro (c.47G>C)?

AlphaMissense predicts likely benign (score 0.1232) — an in-silico prediction, not a clinical call.

P2RX2 p.Arg16Pro

c.47G>C · VCV4691281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1232 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0205%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1232	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -11.45	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.25, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 3,152 bp · p 0.32 · regional, not allelic
Overall
CADD	24.1	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 0.0205% Middle Eastern · 1/4,880 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000187%

Overall 0.000292% 4/1,371,654 alleles · ultra-rare exomes 2/1,221,194 · genomes 2/150,460 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0205%	4,880
African / African-American	0.00302%	33,123
European (non-Finnish)	9.47e-05%	1,055,786

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.Arg16Pro
Coding: c.47G>C
MANE Select: NM_170682
Type: single nucleotide variant
Location: chr12:132618863 (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.Arg16Leu 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-arg16pro (accessed [today's date]).

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