PPP3CA p.Ala447fs
c.1338dup · VCV3900643
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
developmental and epileptic encephalopathy 91
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 12 of 14 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.8, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- PPP3CA
- Protein
- p.Ala447fs
- Coding
- c.1338dup
- MANE Select
- NM_000944
- Type
- Duplication
- Location
- chr4:101032267 (GRCh38)
- Gene constraint
- LOEUF 0.243 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.24 · 21 PDB
- Residue 447
- a UniProt-annotated variant site (in iecee1; results in constitutive phosphatase activity in the absence of calmodulin); a UniProt-annotated variant site (in iecee1); a UniProt-annotated variant site (in iecee1; uncertain significance)
Similar variants
- PPP3CA p.Ala447Thr Pathogenic/Likely pathogenic ★★ ⚠ same residue
- PPP3CA p.Ser438fs Pathogenic/Likely pathogenic ★★ same condition
- PPP3CA p.Thr429fs Pathogenic/Likely pathogenic ★★ same condition
- PPP3CA p.Gly430fs Pathogenic ★ same condition
- PPP3CA p.Ser434fs Pathogenic ★ same condition
- PPP3CA p.Ser446fs Pathogenic ★ same condition
- PPP3CA p.Thr468fs Likely pathogenic ★ same condition
- PPP3CA p.Val420fs Pathogenic ★ same condition
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-ala447fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown