Is PKP2 p.Pro33Ser (c.97C>T) pathogenic?

PKP2 p.Pro33Ser (c.97C>T) is classified Uncertain significance in PKP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-14). AlphaMissense: likely pathogenic (0.8636); No allele count reported in gnomAD v4.1 (AN 1,576,538); Associated with Cardiovascular phenotype.

What condition is associated with PKP2 p.Pro33Ser (c.97C>T)?

PKP2 p.Pro33Ser (c.97C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is PKP2 p.Pro33Ser (c.97C>T) in the general population?

PKP2 p.Pro33Ser (c.97C>T) is no allele count reported in gnomAD v4.1 (AN 1,576,538) (gnomAD).

What do computational predictors say about PKP2 p.Pro33Ser (c.97C>T)?

AlphaMissense predicts likely pathogenic (score 0.8636) — an in-silico prediction, not a clinical call.

PKP2 p.Pro33Ser

c.97C>T · VCV3419524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8636 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,538)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8636	likely pathogenic
REVEL	0.534	indeterminate
SaProt	LLR -5.80	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.0023 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,576,538). 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.Pro33Ser
Coding: c.97C>T
MANE Select: NM_001005242
Type: single nucleotide variant
Location: chr12:32896635 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.32 · 1 PDB
Residue 33: the 'required for interaction with influenza a virus rna polymerase subunit pb1' region; 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

Similar variants

PKP2 p.Pro33= Likely benign ★ same residue
PKP2 c.1034+1G>A Likely pathogenic ★★ same condition
PKP2 c.1034+1G>C Likely pathogenic ★★ same condition
PKP2 c.1170+1G>A Pathogenic/Likely pathogenic ★★ same condition
PKP2 c.1170+2T>A Pathogenic/Likely pathogenic ★★ same condition
PKP2 c.1378+1G>C Pathogenic/Likely pathogenic ★★ same condition
PKP2 c.1378+2T>A Pathogenic/Likely pathogenic ★★ same condition
PKP2 c.1556+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-pro33ser (accessed [today's date]).

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