Is DSP p.Ala1845fs (c.5533del) pathogenic?

DSP p.Ala1845fs (c.5533del) is classified Pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). Associated with arrhythmogenic right ventricular dysplasia 8.

What condition is associated with DSP p.Ala1845fs (c.5533del)?

DSP p.Ala1845fs (c.5533del) is associated with arrhythmogenic right ventricular dysplasia 8 (ClinVar).

DSP p.Ala1845fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.5533del · VCV4532036

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

arrhythmogenic right ventricular dysplasia 8

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	escapes	premature termination codon in the last exon (24 of 24) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1

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

Variant & gene context

Gene: DSP
Protein: p.Ala1845fs
Coding: c.5533del
MANE Select: NM_004415
Type: Deletion
Location: chr6:7582794 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1845: 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

arrhythmogenic right ventricular dysplasia 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

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
DSP p.Asn257fs Pathogenic ★★ same condition
DSP p.Asp1120fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Asp2157fs 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-ala1845fs (accessed [today's date]).

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