PKP2 p.Pro246=
c.738A>G · rs750469808 · VCV3071570
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
1
arrhythmogenic right ventricular 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 -12 | |
| Overall | ||
| CADD | 0.239 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,038 alleles
Overall
6.84e-05%
1/1,461,860 alleles · very rare
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
- PKP2
- Protein
- p.Pro246=
- Coding
- c.738A>G
- MANE Select
- NM_001005242
- dbSNP
- rs750469808
- Type
- single nucleotide variant
- Location
- chr12:32878142 (GRCh38)
- Gene constraint
- LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.32 · 1 PDB
- Residue 246
- the 'required for interaction with influenza a virus rna polymerase subunit pb1' region; a UniProt-annotated variant site (in arvd9; uncertain significance); the 'required for binding to single-stranded dna' region
Similar variants
- PKP2 c.1034+1G>C Likely pathogenic ★★ same condition
- PKP2 c.1170+2T>A Pathogenic/Likely pathogenic ★★ same condition
- PKP2 c.1171-2A>G 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
- PKP2 c.1557-1G>C Pathogenic/Likely pathogenic ★★ same condition
- PKP2 c.2014-1G>C Pathogenic ★★ same condition
- PKP2 c.2167+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-pro246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown