Is P2RX2 p.Pro384Leu (c.1151C>T) pathogenic?

P2RX2 p.Pro384Leu (c.1151C>T) is classified Conflicting classifications of pathogenicity in P2RX2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-23). AlphaMissense: likely benign (0.0966); Ultra-rare (popmax 0.0487%, nfe).

How common is P2RX2 p.Pro384Leu (c.1151C>T) in the general population?

P2RX2 p.Pro384Leu (c.1151C>T) is ultra-rare (popmax 0.0487%, nfe) (gnomAD).

What do computational predictors say about P2RX2 p.Pro384Leu (c.1151C>T)?

AlphaMissense predicts likely benign (score 0.0966) — an in-silico prediction, not a clinical call.

P2RX2 p.Pro384Leu

c.1151C>T · rs148054613 · VCV1599806

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0966 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0487%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0966	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.31	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 1	phastCons 0.071
Regional constraint	o/e 1.04	unconstrained · MANE · 3,152 bp · p 0.32 · regional, not allelic
Overall
CADD	17.02	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 0.0487% European (non-Finnish) · 575/1,179,674 alleles

Filtering AF 0.0454% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0441%

Overall 0.0397% 640/1,613,418 alleles · ultra-rare exomes 594/1,461,096 · genomes 46/152,322 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0544%	1,837
European (non-Finnish)grpmax	0.0487%	2,052
East Asian	0.0379%	2,640
Middle Eastern	0.0165%	6,060
Ashkenazi Jewishnot grpmax-eligible	0.00677%	14,777
African / African-American	0.00666%	15,006
South Asian	0.0044%	22,730
Admixed American	0.00334%	29,968

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro384Leu
Coding: c.1151C>T
MANE Select: NM_170682
dbSNP: rs148054613
Type: single nucleotide variant
Location: chr12:132621707 (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.Pro384= Benign/Likely benign ★★ 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-pro384leu (accessed [today's date]).

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