PPP3CA p.Pro491=
c.1473C>G · rs772699276 · VCV1620145
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, sas)
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 7.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 10.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
South Asian · 10/91,058 alleles
Filtering AF
0.00594%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00453%
Overall
0.000682%
11/1,613,886 alleles · ultra-rare
exomes 11/1,461,702 · genomes 0/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.011% | 9,106 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
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.Pro491=
- Coding
- c.1473C>G
- MANE Select
- NM_000944
- dbSNP
- rs772699276
- Type
- single nucleotide variant
- Location
- chr4:101025958 (GRCh38)
- Gene constraint
- LOEUF 0.243 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.24 · 21 PDB
- Residue 491
- a UniProt-annotated variant site (in iecee1; results in constitutive phosphatase activity in the absence of calmodulin); a UniProt-annotated variant site (in iecee1); the 'disordered' region
Similar variants
- 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
- PPP3CA c.1081+4T>A Uncertain significance ★★ 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-pro491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown