PPP3CA p.Ile81=
c.243T>C · rs538155752 · VCV1629477
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, 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 -5.6 | GERP -5.1 |
| Overall | ||
| CADD | 0.614 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,872 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000186%
3/1,613,926 alleles · very rare
exomes 1/1,461,642 · genomes 2/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,436 |
| Admixed American | 0.00167% | 59,998 |
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.Ile81=
- Coding
- c.243T>C
- MANE Select
- NM_000944
- dbSNP
- rs538155752
- Type
- single nucleotide variant
- Location
- chr4:101195932 (GRCh38)
- Gene constraint
- LOEUF 0.243 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.24 · 21 PDB
- Residue 81
- the 'catalytic' region; a β-strand
Similar variants
- PPP3CA p.Ile81Val 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
- PPP3CA p.His92Arg 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-ile81 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown