PPP3CA p.Ala181=
c.543C>T · rs766502610 · VCV2185886
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00246%, nfe)
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 6.7 | GERP 0.67, phastCons 1 |
| Overall | ||
| CADD | 13.35 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00246%
European (non-Finnish) · 29/1,178,870 alleles
Filtering AF
0.00173%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00149%
Overall
0.00186%
30/1,611,906 alleles · very rare
exomes 28/1,459,806 · genomes 2/152,100 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00246% | 40,651 |
| South Asian | 0.0011% | 90,764 |
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
- PPP3CA
- Protein
- p.Ala181=
- Coding
- c.543C>T
- MANE Select
- NM_000944
- dbSNP
- rs766502610
- Type
- single nucleotide variant
- Location
- chr4:101098466 (GRCh38)
- Gene constraint
- LOEUF 0.243 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.24 · 21 PDB
- Residue 181
- the 'catalytic' region; an α-helix
Similar variants
- PPP3CA p.Ala181Gly Uncertain significance ★ same residue
- PPP3CA p.Ala181Val Uncertain significance ★ ⚠ same residue
- PPP3CA c.1340-2A>G Pathogenic/Likely pathogenic ★★ same type
- PPP3CA p.Ala447Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- PPP3CA p.Arg254Ser Pathogenic/Likely pathogenic ★★ same type
- PPP3CA p.Asp234Glu Pathogenic/Likely pathogenic ★★ same type
- PPP3CA p.Glu282Lys Pathogenic/Likely pathogenic ★★ same type
- PPP3CA p.Glu456Ter 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/ppp3ca-p-ala181 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown