DSP p.Lys2693fs
c.8077_8080del · rs879254352 · VCV246676
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 7.7 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,504 |
| European (non-Finnish)grpmax | 0.00119% | 84,289 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Lys2693fs
- Coding
- c.8077_8080del
- MANE Select
- NM_004415
- dbSNP
- rs879254352
- Type
- Deletion
- Location
- chr6:7585337 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 2693
- 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); a UniProt-annotated variant site (in dcwhk; uncertain significance); an α-helix; the 'binds to telomeres' region; the 'globular 2' region; the '4.5 x 38 aa tandem repeats (domain c)' 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)
Disease context
cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: arrhythmogenic cardiomyopathy with wooly hair and keratodermaarrhythmogenic right ventricular dysplasia 8
For Erythrokeratodermia-cardiomyopathy syndrome (Orphanet):
- Inheritance
- Not applicable
- Onset
- Neonatal
Similar variants
- 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
- DSP p.Asn257fs Pathogenic ★★ same condition
- DSP p.Asp1120fs 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-lys2693fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown