PPP2CA p.Ala140=
c.420A>C · rs373404752 · VCV1299002
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0239%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.29 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.74 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 8.792 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0239%
European (non-Finnish) · 282/1,180,004 alleles
Filtering AF
0.0216%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0206%
Overall
0.0184%
297/1,613,964 alleles · ultra-rare
exomes 284/1,461,738 · genomes 13/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0239% | 4,184 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,463 |
| African / African-American | 0.00133% | 74,922 |
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
- PPP2CA
- Protein
- p.Ala140=
- Coding
- c.420A>C
- MANE Select
- NM_002715
- dbSNP
- rs373404752
- Type
- single nucleotide variant
- Location
- chr5:134201914 (GRCh38)
- Gene constraint
- LOEUF 0.315 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 94.86 · 50 PDB
- Residue 140
- a UniProt-annotated variant site (in hjs3; may be expressed at very low levels, if any); a β-strand
Similar variants
- PPP2CA p.Asp223His Pathogenic/Likely pathogenic ★★ same type
- PPP2CA p.Asp88Gly Pathogenic/Likely pathogenic ★★ same type
- PPP2CA p.Gln122His Likely pathogenic ★★ same type
- PPP2CA p.His191Arg Pathogenic/Likely pathogenic ★★ same type
- PPP2CA p.Tyr127Cys Likely pathogenic ★★ same type
- PPP2CA p.Tyr265Cys Likely pathogenic ★★ same type
- PPP2CA p.Arg108Cys Uncertain significance ★★ ⚠ same type
- PPP2CA p.Asp57Asn 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/ppp2ca-p-ala140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown