PPP2CA p.Leu282=
c.846A>G · rs368267493 · VCV1621992
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00802%, afr)
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 0.84 | GERP -0.55, phastCons 1 |
| Overall | ||
| CADD | 8.262 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00802%
African / African-American · 6/74,790 alleles
Filtering AF
0.00348%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00229%
Overall
0.000622%
10/1,607,442 alleles · very rare
exomes 7/1,455,222 · genomes 3/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00802% | 12,465 |
| European (non-Finnish) | 0.000341% | 293,504 |
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
- PPP2CA
- Protein
- p.Leu282=
- Coding
- c.846A>G
- MANE Select
- NM_002715
- dbSNP
- rs368267493
- Type
- single nucleotide variant
- Location
- chr5:134199097 (GRCh38)
- Gene constraint
- LOEUF 0.315 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 94.86 · 50 PDB
- Residue 282
- 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-leu282 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown