Is PKP2 p.Pro279= (c.837C>T) pathogenic?

PKP2 p.Pro279= (c.837C>T) is classified Conflicting classifications of pathogenicity in PKP2 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-29). Very rare (popmax 0.00329%, sas); Associated with arrhythmogenic right ventricular cardiomyopathy.

What condition is associated with PKP2 p.Pro279= (c.837C>T)?

PKP2 p.Pro279= (c.837C>T) is associated with arrhythmogenic right ventricular cardiomyopathy, cardiomyopathy, arrhythmogenic right ventricular dysplasia 9 (ClinVar).

How common is PKP2 p.Pro279= (c.837C>T) in the general population?

PKP2 p.Pro279= (c.837C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

PKP2 p.Pro279=

c.837C>T · rs572938229 · VCV308513

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

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 -7.7
Overall
CADD	0.713	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,074 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00242% 39/1,613,934 alleles · very rare exomes 36/1,461,590 · genomes 3/152,344 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,358
Remaining individualsnot grpmax-eligible	0.0032%	31,246
European (non-Finnish)	0.00271%	36,876
East Asian	0.00223%	44,880
African / African-American	0.00133%	75,040

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.Pro279=
Coding: c.837C>T
MANE Select: NM_001005242
dbSNP: rs572938229
Type: single nucleotide variant
Location: chr12:32878043 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 1 PDB
Residue 279: 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 cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic right ventricular dysplasia 9

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-pro279 (accessed [today's date]).

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