Is PKP2 p.Ser44Pro (c.130_131delinsCC) pathogenic?

PKP2 p.Ser44Pro (c.130131delinsCC) is classified Uncertain significance in PKP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-07). No gnomAD frequency available for this variant; Associated with arrhythmogenic right ventricular dysplasia 9.

What condition is associated with PKP2 p.Ser44Pro (c.130_131delinsCC)?

PKP2 p.Ser44Pro (c.130_131delinsCC) is associated with arrhythmogenic right ventricular dysplasia 9 (ClinVar).

How common is PKP2 p.Ser44Pro (c.130_131delinsCC) in the general population?

PKP2 p.Ser44Pro (c.130_131delinsCC) is no gnomAD frequency available for this variant (gnomAD).

PKP2 p.Ser44Pro

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.130_131delinsCC · rs2541384544 · VCV1769387

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 2	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.0023 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PKP2
Protein: p.Ser44Pro
Coding: c.130_131delinsCC
MANE Select: NM_001005242
dbSNP: rs2541384544
Type: Indel
Location: chr12:32896601 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 1 PDB
Residue 44: the 'required for interaction with influenza a virus rna polymerase subunit pb1' region; a modified residue (phosphoserine); 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

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

PKP2 p.Ser44Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
PKP2 p.Asn771fs Pathogenic/Likely pathogenic ★★ same condition
PKP2 p.Leu436fs Pathogenic/Likely pathogenic ★★ same condition
PKP2 p.Pro735fs Pathogenic/Likely pathogenic ★★ same condition
PKP2 p.Ala705Ile Uncertain significance ★★ same condition
PKP2 p.Ser44Arg Uncertain significance ★★ ⚠ same residue
PKP2 c.2358-1_2358delinsTT Likely pathogenic ★ same condition
PKP2 p.Glu561Ter 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-ser44pro (accessed [today's date]).

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