PPP2CA p.Arg214Ter
c.640C>T · rs148071386 · VCV70140
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Houge-Janssens syndrome 3
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 5 of 7 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 40.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- PPP2CA
- Protein
- p.Arg214Ter
- Coding
- c.640C>T
- MANE Select
- NM_002715
- dbSNP
- rs148071386
- Type
- single nucleotide variant
- Location
- chr5:134200433 (GRCh38)
- Gene constraint
- LOEUF 0.315 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 94.86 · 50 PDB
- Residue 214
- 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 condition
- PPP2CA p.Asp88Gly Pathogenic/Likely pathogenic ★★ same condition
- PPP2CA p.Gln122His Likely pathogenic ★★ same condition
- PPP2CA p.His191Arg Pathogenic/Likely pathogenic ★★ same condition
- PPP2CA p.Tyr127Cys Likely pathogenic ★★ same condition
- PPP2CA p.Tyr265Cys Likely pathogenic ★★ same condition
- PPP2CA p.Ser171Leu Uncertain significance ★★ ⚠ same condition
- PPP2CA c.-37C>G Benign ★★ same condition
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-arg214ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown