Is DSP p.Lys1676fs (c.5024_5027dup) pathogenic?

DSP p.Lys1676fs (c.50245027dup) is classified Likely pathogenic in DSP (ClinVar, Single submitter, 1 submitter). Associated with cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis.

What condition is associated with DSP p.Lys1676fs (c.5024_5027dup)?

DSP p.Lys1676fs (c.5024_5027dup) 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.Lys1676fs

c.5024_5027dup · VCV3382407

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 23 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.6	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DSP
Protein: p.Lys1676fs
Coding: c.5024_5027dup
MANE Select: NM_004415
Type: Duplication
Location: chr6:7581213 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1676: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance; abolishes expression in the myocardium); the 'central fibrous rod domain' region; the 'binds to telomeres' region; 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); a UniProt-annotated variant site (in arvd8)

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.Glu310fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Ile950fs Pathogenic/Likely pathogenic ★★ same condition
DSP c.2631-13dup Uncertain significance ★★ same condition
DSP p.Asn1364fs Likely pathogenic ★ same condition
DSP p.Leu764fs Likely pathogenic ★ same condition
DSP p.Lys1676= Likely benign ★ same residue
DSP p.Arg606_Ala615dup Pathogenic same condition
DSP c.2131_2132del 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/dsp-p-lys1676fs (accessed [today's date]).

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