Is PKP2 p.Ser802Pro (c.2404T>C) pathogenic?

PKP2 p.Ser802Pro (c.2404T>C) is classified Uncertain significance in PKP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-10). AlphaMissense: likely pathogenic (0.9674); Absent from gnomAD v4.1; Associated with arrhythmogenic right ventricular dysplasia 9.

What condition is associated with PKP2 p.Ser802Pro (c.2404T>C)?

PKP2 p.Ser802Pro (c.2404T>C) is associated with arrhythmogenic right ventricular dysplasia 9 (ClinVar).

How common is PKP2 p.Ser802Pro (c.2404T>C) in the general population?

PKP2 p.Ser802Pro (c.2404T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PKP2 p.Ser802Pro (c.2404T>C)?

AlphaMissense predicts likely pathogenic (score 0.9674) — an in-silico prediction, not a clinical call.

PKP2 p.Ser802Pro

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.2404T>C · rs1183143350 · VCV1362428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9674 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

arrhythmogenic right ventricular dysplasia 9

Computational evidence

Protein change
AlphaMissense	0.9674	likely pathogenic · top 6% in PKP2
REVEL	0.269	benign-leaning
SaProt	LLR -14.07	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.0023 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S846P vs ClinVar S802P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PKP2
Protein: p.Ser802Pro
Coding: c.2404T>C
MANE Select: NM_001005242
dbSNP: rs1183143350
Type: single nucleotide variant
Location: chr12:32792685 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 1 PDB
Residue 846 UniProt numbering: a UniProt-annotated variant site (in arvd9; uncertain significance)

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.Ser802Ala Uncertain significance ★★ ⚠ same residue
PKP2 p.Ser802Phe Uncertain significance ★★ ⚠ same residue
PKP2 p.Ser802Tyr Uncertain significance ★★ ⚠ same residue
PKP2 p.Ser802fs Pathogenic ★ same residue
PKP2 p.Ser802Cys 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

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-ser802pro (accessed [today's date]).

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