Is DSP p.Leu764fs (c.2290_2291dup) pathogenic?

DSP p.Leu764fs (c.22902291dup) is classified Likely pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-18). Absent from gnomAD; Associated with cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis.

What condition is associated with DSP p.Leu764fs (c.2290_2291dup)?

DSP p.Leu764fs (c.2290_2291dup) is associated with cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis (ClinVar).

How common is DSP p.Leu764fs (c.2290_2291dup) in the general population?

DSP p.Leu764fs (c.2290_2291dup) is absent from gnomAD (gnomAD).

How is Erythrokeratodermia-cardiomyopathy syndrome inherited?

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

DSP p.Leu764fs

c.2290_2291dup · rs2533903987 · VCV2628093

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 16 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.11	GERP -2.1, phastCons 0.92

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: DSP
Protein: p.Leu764fs
Coding: c.2290_2291dup
MANE Select: NM_004415
dbSNP: rs2533903987
Type: Duplication
Location: chr6:7574244 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 764: a UniProt-annotated variant site (in arvd8; uncertain significance); the 'globular 1' region; the 'interaction with mapre1' region; 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); 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.Lys1676fs Likely pathogenic ★ same condition
DSP p.Arg606_Ala615dup Pathogenic same condition
DSP c.2131_2132del Pathogenic/Likely pathogenic ★★ same condition
DSP c.422+1G>A 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-leu764fs (accessed [today's date]).

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