PKP2 p.Pro699=
c.2097A>G · rs780623116 · VCV2774081
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000508%, nfe)
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 -2.1 | |
| Overall | ||
| CADD | 0.525 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000508%
European (non-Finnish) · 6/1,179,966 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.00041%
6/1,461,824 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.Pro699=
- Coding
- c.2097A>G
- MANE Select
- NM_001005242
- dbSNP
- rs780623116
- Type
- single nucleotide variant
- Location
- chr12:32802473 (GRCh38)
- Gene constraint
- LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.32 · 1 PDB
- Residue 699
- a UniProt-annotated variant site (in arvd9; uncertain significance)
Similar variants
- PKP2 p.Pro699_Ser700insArg 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-pro699 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown