P2RX2 p.Pro434=
c.1302G>A · rs114276183 · VCV226979
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.14%, afr)
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 -3.3 | |
| Overall | ||
| CADD | 3.723 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.14%
African / African-American · 3,105/75,012 alleles
Filtering AF
4.02%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.97%
Overall
0.219%
3,531/1,612,918 alleles · low-frequency
exomes 1,739/1,460,696 · genomes 1,792/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.14% | 24 |
| Admixed American | 0.284% | 353 |
| Remaining individualsnot grpmax-eligible | 0.271% | 370 |
| Middle Eastern | 0.099% | 1,010 |
| South Asian | 0.011% | 9,100 |
| European (non-Finnish) | 0.00576% | 17,348 |
| East Asian | 0.00446% | 22,435 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,540 |
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.Pro434=
- Coding
- c.1302G>A
- MANE Select
- NM_170682
- dbSNP
- rs114276183
- Type
- single nucleotide variant
- Location
- chr12:132621858 (GRCh38)
- Gene constraint
- LOEUF 1.276 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.80 · 18 PDB
- Residue 434
- the 'disordered' region
Similar variants
- 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
- P2RX2 p.Asp180Asn 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-pro434 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown