Is PKP2 p.Pro191= (c.573A>C) pathogenic?

PKP2 p.Pro191= (c.573A>C) is classified Likely benign in PKP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-03). Very rare (popmax 0.00134%, afr); Associated with arrhythmogenic right ventricular dysplasia 9.

What condition is associated with PKP2 p.Pro191= (c.573A>C)?

PKP2 p.Pro191= (c.573A>C) is associated with arrhythmogenic right ventricular dysplasia 9, cardiomyopathy (ClinVar).

How common is PKP2 p.Pro191= (c.573A>C) in the general population?

PKP2 p.Pro191= (c.573A>C) is very rare (popmax 0.00134%, afr) (gnomAD).

PKP2 p.Pro191=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.573A>C · VCV4757523

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

arrhythmogenic right ventricular dysplasia 9

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 -11
Overall
CADD	0.255	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,898 alleles

Overall 6.2e-05% 1/1,613,146 alleles · very rare exomes 0/1,461,060 · genomes 1/152,086 · joint denominator

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.Pro191=
Coding: c.573A>C
MANE Select: NM_001005242
Type: single nucleotide variant
Location: chr12:32878307 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 1 PDB
Residue 191: 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

Full PKP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

arrhythmogenic right ventricular dysplasia 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

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-pro191 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown