PIEZO2 p.Pro423=
c.1269C>T · rs1405916857 · VCV747504
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, 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 -10 | GERP -3.2 |
| Overall | ||
| CADD | 0.742 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
Admixed American · 10/50,516 alleles
Filtering AF
0.0107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00816%
Overall
0.00124%
19/1,534,784 alleles · ultra-rare
exomes 17/1,382,644 · genomes 2/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0198% | 5,052 |
| Remaining individualsnot grpmax-eligible | 0.00334% | 29,963 |
| African / African-American | 0.00137% | 72,904 |
| South Asian | 0.0012% | 83,582 |
| European (non-Finnish) | 0.000436% | 229,196 |
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.Pro423=
- Coding
- c.1269C>T
- MANE Select
- NM_001378183
- dbSNP
- rs1405916857
- Type
- single nucleotide variant
- Location
- chr18:10800446 (GRCh38)
- Gene constraint
- LOEUF 0.563 · pLI <0.01 (gnomAD)
Similar variants
- 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
- PIEZO2 p.Arg2799Cys Pathogenic/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-pro423 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown