PPP3CA p.Ala83=
c.249G>A · rs3730251 · VCV1290046
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 20.6%, 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 | GERP -5.1 |
| Overall | ||
| CADD | 5.712 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
20.6%
African / African-American · 15,422/74,910 alleles
Filtering AF
20.3%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 20.2%
Overall
1.36%
21,985/1,613,482 alleles · common
exomes 12,545/1,461,318 · genomes 9,440/152,164 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 20.6% | 5 |
| East Asian | 2.52% | 40 |
| Middle Eastern | 2.21% | 45 |
| Admixed American | 1.91% | 52 |
| Remaining individualsnot grpmax-eligible | 1.91% | 52 |
| South Asian | 0.839% | 119 |
| European (non-Finnish) | 0.183% | 546 |
| Ashkenazi Jewishnot grpmax-eligible | 0.105% | 953 |
| Finnishnot grpmax-eligible | 0.00625% | 15,993 |
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.Ala83=
- Coding
- c.249G>A
- MANE Select
- NM_000944
- dbSNP
- rs3730251
- Type
- single nucleotide variant
- Location
- chr4:101195926 (GRCh38)
- Gene constraint
- LOEUF 0.243 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.24 · 21 PDB
- Residue 83
- the 'catalytic' region; a β-strand
Similar variants
- PPP3CA p.Ala83Val 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-ala83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown