PKP2 p.Leu730=
c.2190G>A · rs886049320 · VCV308506
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Conditions
2
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 3.1 | phastCons 1 |
| Overall | ||
| CADD | 11.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/90,724 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000275%
4/1,456,310 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 90,724 |
| European (non-Finnish) | 0.000255% | 391,784 |
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.Leu730=
- Coding
- c.2190G>A
- MANE Select
- NM_001005242
- dbSNP
- rs886049320
- Type
- single nucleotide variant
- Location
- chr12:32796276 (GRCh38)
- Gene constraint
- LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.32 · 1 PDB
- Residue 730
- a UniProt-annotated variant site (in arvd9; uncertain significance)
Similar variants
- PKP2 c.1034+1G>C Likely pathogenic ★★ same condition
- PKP2 c.1034+1G>T Likely pathogenic ★★ same condition
- PKP2 c.1035-2A>G Likely pathogenic ★★ same condition
- PKP2 c.1170+1G>A Pathogenic/Likely pathogenic ★★ same condition
- PKP2 c.1170+1G>C 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>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-leu730 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown