PPP3CA p.Ser434=
c.1302C>T · rs369318194 · VCV1458785
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00168%, amr)
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 0.2 | GERP -5.6, phastCons 0.84 |
| Overall | ||
| CADD | 12.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00168%
Admixed American · 1/59,696 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000559%
9/1,611,024 alleles · very rare
exomes 7/1,458,868 · genomes 2/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00168% | 59,696 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,346 |
| African / African-American | 0.00134% | 74,786 |
| South Asian | 0.0011% | 90,622 |
| European (non-Finnish) | 0.000424% | 235,709 |
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.Ser434=
- Coding
- c.1302C>T
- MANE Select
- NM_000944
- dbSNP
- rs369318194
- Type
- single nucleotide variant
- Location
- chr4:101032304 (GRCh38)
- Gene constraint
- LOEUF 0.243 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.24 · 21 PDB
Similar variants
- PPP3CA p.Ser434Arg Uncertain significance ★★ ⚠ same residue
- PPP3CA p.Ser434Thr Uncertain significance ★ ⚠ same residue
- PPP3CA p.Ser434fs Pathogenic ★ 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
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-ser434 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown