PPP2CA p.Thr227=
c.681A>G · rs1278766294 · VCV1565910
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00102%, nfe)
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 0.67 | GERP 0.71, phastCons 1 |
| Overall | ||
| CADD | 10.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00102%
European (non-Finnish) · 12/1,180,042 alleles
Filtering AF
0.000542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000428%
Overall
0.000743%
12/1,614,094 alleles · very rare
exomes 10/1,461,862 · genomes 2/152,232 · joint denominator
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.Thr227=
- Coding
- c.681A>G
- MANE Select
- NM_002715
- dbSNP
- rs1278766294
- Type
- single nucleotide variant
- Location
- chr5:134200392 (GRCh38)
- Gene constraint
- LOEUF 0.315 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 94.86 · 50 PDB
- Residue 227
- 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); an α-helix
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-thr227 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown