Is DSP p.Ile1359fs (c.4076_4106del) pathogenic?

DSP p.Ile1359fs (c.40764106del) is classified Pathogenic/Likely pathogenic in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-15). Absent from gnomAD; Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

How common is DSP p.Ile1359fs (c.4076_4106del) in the general population?

DSP p.Ile1359fs (c.4076_4106del) is absent from gnomAD (gnomAD).

How is Carvajal syndrome inherited?

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

DSP p.Ile1359fs

Q: What condition is associated with DSP p.Ile1359fs (c.4076_4106del)?

DSP p.Ile1359fs (c.4076_4106del) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.4076_4106del · rs2533927331 · VCV1964246

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

arrhythmogenic cardiomyopathy with wooly hair and keratoderma

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 9.3	GERP 1.6, phastCons 1

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.Ile1359fs
Coding: c.4076_4106del
MANE Select: NM_004415
dbSNP: rs2533927331
Type: Deletion
Location: chr6:7580264 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1359: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); 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

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

Also linked: arrhythmogenic right ventricular dysplasia 8

For Carvajal syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

DSP p.Ile1359= Likely benign ★★ same residue
DSP p.Ile1359Met Uncertain significance ★ same residue
DSP c.2131-3_2131del Likely pathogenic ★★ same condition
DSP p.Ala2092fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1113fs Pathogenic ★★ same condition
DSP p.Arg1173fs Pathogenic ★★ same condition
DSP p.Arg1506fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Asn1346fs 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-ile1359fs (accessed [today's date]).

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