Is DSP p.Arg1123fs (c.3368_3372del) pathogenic?

DSP p.Arg1123fs (c.33683372del) is classified Likely pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-19). Absent from gnomAD; Associated with arrhythmogenic right ventricular dysplasia 8.

What condition is associated with DSP p.Arg1123fs (c.3368_3372del)?

DSP p.Arg1123fs (c.3368_3372del) is associated with arrhythmogenic right ventricular dysplasia 8 (ClinVar).

How common is DSP p.Arg1123fs (c.3368_3372del) in the general population?

DSP p.Arg1123fs (c.3368_3372del) is absent from gnomAD (gnomAD).

DSP p.Arg1123fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.3368_3372del · rs2533923368 · VCV2628095

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

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	predicted	premature termination codon in exon 23 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.43	GERP -2.7, phastCons 0.001

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.Arg1123fs
Coding: c.3368_3372del
MANE Select: NM_004415
dbSNP: rs2533923368
Type: Deletion
Location: chr6:7579554 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1123: 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 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-arg1123fs (accessed [today's date]).

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