Is PKP2 p.Pro273= (c.819G>A) pathogenic?

PKP2 p.Pro273= (c.819G>A) is classified Benign in PKP2 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 8.81%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with PKP2 p.Pro273= (c.819G>A)?

PKP2 p.Pro273= (c.819G>A) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic right ventricular dysplasia 9 (ClinVar).

PKP2 p.Pro273=

Q: How common is PKP2 p.Pro273= (c.819G>A) in the general population?

PKP2 p.Pro273= (c.819G>A) is common (popmax 8.81%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.819G>A · rs3748279 · VCV45086

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 8.81%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

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 -20
Overall
CADD	0.568	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.81% East Asian · 3,953/44,882 alleles

Filtering AF 8.58% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.48%

Overall 0.275% 4,431/1,613,946 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	8.81%	11
Remaining individualsnot grpmax-eligible	0.501%	200
South Asian	0.0933%	1,071
Middle Eastern	0.051%	1,961
Admixed American	0.03%	3,335
African / African-American	0.0226%	4,416
European (non-Finnish)	0.00347%	28,781
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

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.Pro273=
Coding: c.819G>A
MANE Select: NM_001005242
dbSNP: rs3748279
Type: single nucleotide variant
Location: chr12:32878061 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 1 PDB
Residue 273: 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

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

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

Similar variants

PKP2 p.Pro273Leu Uncertain significance ★★ ⚠ same residue
PKP2 c.1034+1G>A Likely pathogenic ★★ same condition
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

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-pro273 (accessed [today's date]).

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