PIEZO2 p.Ser331=
c.993G>A · VCV3710920
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.315%, eas)
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 -3.9 | GERP -3.4 |
| Overall | ||
| CADD | 4.919 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.315%
East Asian · 129/40,912 alleles
Filtering AF
0.271%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.254%
Overall
0.0102%
157/1,537,188 alleles · rare
exomes 145/1,384,910 · genomes 12/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.315% | 317 |
| Middle Eastern | 0.0334% | 2,995 |
| African / African-American | 0.00273% | 36,578 |
| Finnishnot grpmax-eligible | 0.00219% | 45,608 |
| Admixed American | 0.00196% | 50,988 |
| European (non-Finnish) | 0.00174% | 57,344 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 60,042 |
| South Asian | 0.00119% | 84,056 |
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.Ser331=
- Coding
- c.993G>A
- MANE Select
- NM_001378183
- Type
- single nucleotide variant
- Location
- chr18:10807199 (GRCh38)
- Gene constraint
- LOEUF 0.563 · pLI <0.01 (gnomAD)
Similar variants
- PIEZO2 p.Ser331Leu Benign ★ 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-ser331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown