Is DSP p.Ser1894fs (c.5680_5683del) pathogenic?

DSP p.Ser1894fs (c.56805683del) is classified Pathogenic/Likely pathogenic in DSP (ClinVar, Multiple submitters, 11 submitters; last evaluated 2025-12-04). Very rare (popmax 0.005%, amr); Associated with DSP-related disorder.

What condition is associated with DSP p.Ser1894fs (c.5680_5683del)?

DSP p.Ser1894fs (c.5680_5683del) is associated with DSP-related disorder, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Ser1894fs (c.5680_5683del) in the general population?

DSP p.Ser1894fs (c.5680_5683del) is very rare (popmax 0.005%, amr) (gnomAD).

DSP p.Ser1894fs

c.5680_5683del · rs774763657 · VCV405232

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

DSP-related disorder

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 4.1	GERP 1.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,012 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000205% 3/1,461,870 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DSP
Protein: p.Ser1894fs
Coding: c.5680_5683del
MANE Select: NM_004415
dbSNP: rs774763657
Type: Deletion
Location: chr6:7582941 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1894: 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

DSP-related disorder

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8 lethal acantholytic epidermolysis bullosa keratosis palmoplantaris striata 2 cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis familial isolated arrhythmogenic right ventricular dysplasia

Similar variants

DSP p.Ser1894Arg Uncertain significance ★ ⚠ same residue
DSP p.Ser1894Thr 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-ser1894fs (accessed [today's date]).

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