PKP2 p.Ala559=
c.1677C>T · VCV4756234
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
cardiomyopathy
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 3.7 | phastCons 1 |
| Overall | ||
| CADD | 10.91 | PHRED · no single calibrated threshold — expert panels disagree |
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
- PKP2
- Protein
- p.Ala559=
- Coding
- c.1677C>T
- MANE Select
- NM_001005242
- Type
- single nucleotide variant
- Location
- chr12:32822629 (GRCh38)
- Gene constraint
- LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.32 · 1 PDB
- Residue 559
- a UniProt-annotated variant site (in arvd9; uncertain significance); an α-helix
Similar variants
- PKP2 p.Ala559Thr Uncertain significance ★ ⚠ same residue
- PKP2 c.1034+1G>C Likely pathogenic ★★ same condition
- PKP2 c.1034+1G>T Likely pathogenic ★★ same condition
- PKP2 c.1170+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PKP2 c.1171-2A>G Pathogenic/Likely pathogenic ★★ same condition
- PKP2 c.1378+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PKP2 c.1378+1G>C Pathogenic/Likely pathogenic ★★ same condition
- PKP2 c.1556+1G>A Pathogenic/Likely pathogenic ★★ 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/pkp2-p-ala559 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown