Is DSP p.Leu319del (c.955_957del) pathogenic?

DSP p.Leu319del (c.955957del) is classified Likely pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). Associated with cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis.

What condition is associated with DSP p.Leu319del (c.955_957del)?

DSP p.Leu319del (c.955_957del) is associated with cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis (ClinVar).

How is Erythrokeratodermia-cardiomyopathy syndrome inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

DSP p.Leu319del

c.955_957del · VCV3544418

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis

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 0.98	GERP -3.8, phastCons 0.99

Variant & gene context

Gene: DSP
Protein: p.Leu319del
Coding: c.955_957del
MANE Select: NM_004415
Type: Deletion
Location: chr6:7566392 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 319: an α-helix; the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; the 'interaction with pkp1' region; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in arvd8; likely pathogenic; results in an unstable protein that forms perinuclear aggregates); a UniProt-annotated variant site (in arvd8 and dcwhkta; uncertain significance)

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

Disease context

cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Erythrokeratodermia-cardiomyopathy syndrome (Orphanet):

Inheritance: Not applicable
Onset: Neonatal

Similar variants

DSP p.Asn1346fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Gln948fs Pathogenic ★★ same condition
DSP p.Leu2031fs Pathogenic ★★ same condition
DSP p.Lys2693fs Pathogenic ★★ same condition
DSP p.Ser1894fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Ser1588del Uncertain significance ★★ same condition
DSP p.Leu319= Likely benign ★★ same residue
DSP p.Asp1470fs 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/dsp-p-leu319del (accessed [today's date]).

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