Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 10.6%, afr) — too common for a highly-penetrant pathogenic allele
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 -6.3 | GERP -3.7 |
| Overall | ||
| CADD | 6.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
10.6%
African / African-American · 7,732/73,062 alleles
Filtering AF
10.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.3%
Overall
0.587%
9,013/1,536,356 alleles · common
exomes 4,386/1,384,154 · genomes 4,627/152,202 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 10.6% | 9 |
| Remaining individualsnot grpmax-eligible | 0.798% | 125 |
| Admixed American | 0.775% | 129 |
| Middle Eastern | 0.718% | 139 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0908% | 1,102 |
| European (non-Finnish) | 0.0266% | 3,759 |
| South Asian | 0.025% | 4,002 |
| East Asian | 0.0147% | 6,819 |
| Finnishnot grpmax-eligible | 0.0133% | 7,546 |
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
- PIEZO2
- Protein
- p.Pro239=
- Coding
- c.717G>A
- MANE Select
- NM_001378183
- dbSNP
- rs8085615
- Type
- single nucleotide variant
- Location
- chr18:10855553 (GRCh38)
- Gene constraint
- LOEUF 0.563 · pLI <0.01 (gnomAD)
Similar variants
- PIEZO2 p.Pro239Leu Uncertain significance ★★ ⚠ same residue
- PIEZO2 c.1528-1G>A Likely pathogenic ★★ same type
- PIEZO2 c.4708+2T>G Likely pathogenic ★★ same type
- PIEZO2 c.5257-1G>A Pathogenic ★★ same type
- PIEZO2 c.7686+1G>C Likely pathogenic ★★ same type
- PIEZO2 p.Arg1600Ter Pathogenic/Likely pathogenic ★★ same type
- PIEZO2 p.Arg1743Ter Pathogenic/Likely pathogenic ★★ same type
- PIEZO2 p.Arg26Ter Likely pathogenic ★★ 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/piezo2-p-pro239 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown