PPP2CA p.Asp279=
c.837C>T · rs201998249 · VCV1611135
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.744%, 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 1.1 | GERP -1.8, phastCons 0.99 |
| Overall | ||
| CADD | 11.38 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.744%
South Asian · 677/91,010 alleles
Filtering AF
0.697%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.679%
Overall
0.061%
982/1,610,922 alleles · rare
exomes 906/1,458,674 · genomes 76/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.744% | 134 |
| Middle Eastern | 0.314% | 319 |
| Remaining individualsnot grpmax-eligible | 0.0865% | 1,156 |
| European (non-Finnish) | 0.0184% | 5,425 |
| Admixed American | 0.01% | 10,001 |
| African / African-American | 0.00801% | 12,489 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,588 |
| East Asian | 0.00223% | 44,870 |
| Finnishnot grpmax-eligible | 0.00156% | 64,002 |
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.Asp279=
- Coding
- c.837C>T
- MANE Select
- NM_002715
- dbSNP
- rs201998249
- Type
- single nucleotide variant
- Location
- chr5:134199106 (GRCh38)
- Gene constraint
- LOEUF 0.315 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 94.86 · 50 PDB
- Residue 279
- a UniProt-annotated variant site (in hjs3; may be expressed at very low levels, if any); a UniProt-annotated variant site (in hjs3; loss of phosphatase activity in an in vitro assay; complete loss of interaction with pp2a subunit a ppp2r1a/ppp2r1b; interacts with alpha4/igbp1; loss of interaction with pp2a subunit b components)
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-asp279 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown