Is DSP p.Leu2368fs (c.7103dup) pathogenic?

DSP p.Leu2368fs (c.7103dup) is classified Likely pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Leu2368fs (c.7103dup)?

DSP p.Leu2368fs (c.7103dup) is associated with Cardiovascular phenotype (ClinVar).

DSP p.Leu2368fs

c.7103dup · VCV3767932

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Cardiovascular phenotype

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 -1.2	GERP -1.6

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

Variant & gene context

Gene: DSP
Protein: p.Leu2368fs
Coding: c.7103dup
MANE Select: NM_004415
Type: Duplication
Location: chr6:7584363 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2368: 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); a UniProt-annotated variant site (in ebla; uncertain significance); an α-helix; the 'binds to telomeres' region; the 'globular 2' region; the '4.5 x 38 aa tandem repeats (domain b)' 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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSP p.Asn1234fs Pathogenic ★★ same condition
DSP p.Gln1467fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Gln216fs Pathogenic ★★ same condition
DSP p.Gln873fs Pathogenic ★★ same condition
DSP p.Gln994fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Glu1159fs Pathogenic ★★ same condition
DSP p.Glu310fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Ile238fs 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-leu2368fs (accessed [today's date]).

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