Is PKP2 p.Pro367= (c.1101A>G) pathogenic?

PKP2 p.Pro367= (c.1101A>G) is classified Likely benign in PKP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-03-04). Very rare (popmax 0.00446%, eas); Associated with cardiomyopathy.

How common is PKP2 p.Pro367= (c.1101A>G) in the general population?

PKP2 p.Pro367= (c.1101A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

PKP2 p.Pro367=

Q: What condition is associated with PKP2 p.Pro367= (c.1101A>G)?

PKP2 p.Pro367= (c.1101A>G) is associated with cardiomyopathy, arrhythmogenic right ventricular dysplasia 9, arrhythmogenic right ventricular cardiomyopathy (ClinVar).

c.1101A>G · rs776927054 · VCV629713

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

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 -13
Overall
CADD	0.068	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,888 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00031% 5/1,613,964 alleles · very rare exomes 5/1,461,604 · genomes 0/152,360 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,444
South Asian	0.0022%	45,534
European (non-Finnish)	8.48e-05%	1,179,902

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.Pro367=
Coding: c.1101A>G
MANE Select: NM_001005242
dbSNP: rs776927054
Type: single nucleotide variant
Location: chr12:32868996 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 1 PDB
Residue 367: a UniProt-annotated variant site (in arvd9; uncertain significance); an α-helix

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

Disease context

cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: arrhythmogenic right ventricular dysplasia 9 arrhythmogenic right ventricular cardiomyopathy

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-pro367 (accessed [today's date]).

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