P2RX2 p.Pro406=
c.1218C>T · VCV4919236
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.027%, amr)
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 -1.8 | |
| Overall | ||
| CADD | 6.204 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.027%
Admixed American · 16/59,164 alleles
Filtering AF
0.0213%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0204%
Overall
0.0197%
316/1,600,470 alleles · ultra-rare
exomes 302/1,448,100 · genomes 14/152,370 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.027% | 3,698 |
| European (non-Finnish) | 0.0236% | 4,246 |
| East Asian | 0.0157% | 6,389 |
| Remaining individualsnot grpmax-eligible | 0.0097% | 10,311 |
| African / African-American | 0.00935% | 10,692 |
| South Asian | 0.00336% | 29,737 |
| Finnishnot grpmax-eligible | 0.00158% | 63,170 |
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.Pro406=
- Coding
- c.1218C>T
- MANE Select
- NM_170682
- Type
- single nucleotide variant
- Location
- chr12:132621774 (GRCh38)
- Gene constraint
- LOEUF 1.276 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.80 · 18 PDB
- Residue 406
- 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-pro406 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown