Is PKP1 p.Pro5= (c.15G>T) pathogenic?

PKP1 p.Pro5= (c.15G>T) is classified Uncertain significance in PKP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Rare (popmax 0.183%, eas); Associated with epidermolysis bullosa simplex due to plakophilin deficiency.

What condition is associated with PKP1 p.Pro5= (c.15G>T)?

PKP1 p.Pro5= (c.15G>T) is associated with epidermolysis bullosa simplex due to plakophilin deficiency (ClinVar).

How common is PKP1 p.Pro5= (c.15G>T) in the general population?

PKP1 p.Pro5= (c.15G>T) is rare (popmax 0.183%, eas) (gnomAD).

How is Ectodermal dysplasia-skin fragility syndrome inherited?

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

PKP1 p.Pro5=

c.15G>T · rs760122260 · VCV294799

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.183%, eas)

Conditions

epidermolysis bullosa simplex due to plakophilin deficiency

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 0.16	GERP -2.7, phastCons 0.87
Overall
CADD	12.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.183% East Asian · 82/44,862 alleles

Filtering AF 0.151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.00521% 84/1,613,612 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.183%	547
Remaining individualsnot grpmax-eligible	0.0032%	31,234

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: PKP1
Protein: p.Pro5=
Coding: c.15G>T
MANE Select: NM_001005337
dbSNP: rs760122260
Type: single nucleotide variant
Location: chr1:201283717 (GRCh38)
Gene constraint: LOEUF 0.499 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 68.91 · 1 PDB
Residue 5: the 'required for interaction with eif4a1' region; the 'required for binding to single stranded dna' region

Full PKP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epidermolysis bullosa simplex due to plakophilin deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ectodermal dysplasia-skin fragility syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

PKP1 p.Ala480Thr Uncertain significance ★★ ⚠ same condition
PKP1 p.Arg332His Uncertain significance ★★ ⚠ same condition
PKP1 p.Arg378Cys Uncertain significance ★★ ⚠ same condition
PKP1 p.Arg420Cys Uncertain significance ★★ ⚠ same condition
PKP1 p.Arg645Lys Uncertain significance ★★ ⚠ same condition
PKP1 p.Asn646Lys Uncertain significance ★★ ⚠ same condition
PKP1 p.Lys151Asn Uncertain significance ★★ ⚠ same condition
PKP1 p.Met46Leu Uncertain significance ★★ ⚠ 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/pkp1-p-pro5 (accessed [today's date]).

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