Is PKP2 p.Ser313= (c.939C>T) pathogenic?

PKP2 p.Ser313= (c.939C>T) is classified Benign/Likely benign in PKP2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-03). Rare (popmax 0.774%, afr); Associated with cardiomyopathy.

What condition is associated with PKP2 p.Ser313= (c.939C>T)?

PKP2 p.Ser313= (c.939C>T) is associated with cardiomyopathy, arrhythmogenic right ventricular dysplasia 9 (ClinVar).

How common is PKP2 p.Ser313= (c.939C>T) in the general population?

PKP2 p.Ser313= (c.939C>T) is rare (popmax 0.774%, afr) (gnomAD).

PKP2 p.Ser313=

c.939C>T · rs61729381 · VCV45089

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.774%, afr)

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 -0.56
Overall
CADD	5.912	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.774% African / African-American · 581/75,046 alleles

Filtering AF 0.722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.701%

Overall 0.0398% 643/1,614,114 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.774%	129
Admixed American	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.0368%	2,718
European (non-Finnish)	0.000593%	168,574

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.Ser313=
Coding: c.939C>T
MANE Select: NM_001005242
dbSNP: rs61729381
Type: single nucleotide variant
Location: chr12:32877941 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 1 PDB
Residue 313: the 'required for interaction with influenza a virus rna polymerase subunit pb1' region; the 'disordered' 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

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

Also linked: arrhythmogenic right ventricular dysplasia 9

Similar variants

PKP2 p.Ser313fs Likely pathogenic ★ same residue
PKP2 p.Ser313Arg Uncertain significance ★ ⚠ same residue
PKP2 p.Ser313Asn Uncertain significance ★ ⚠ same residue
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

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-ser313 (accessed [today's date]).

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