DSP p.Ile679fs
c.2036_2039del · VCV4794761
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 15 of 24 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 1.8, 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% | 62,508 |
| European (non-Finnish)grpmax | 8.47e-05% | 1,180,020 |
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.Ile679fs
- Coding
- c.2036_2039del
- MANE Select
- NM_004415
- Type
- Deletion
- Location
- chr6:7571971 (GRCh38)
- Gene constraint
- LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 679
- a UniProt-annotated variant site (in arvd8; uncertain significance); the 'globular 1' region; the 'interaction with mapre1' region; a UniProt-annotated variant site (in dcwhkta; uncertain significance); 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
arrhythmogenic right ventricular dysplasia 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: arrhythmogenic cardiomyopathy with wooly hair and keratoderma
For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- No data available
Similar variants
- DSP p.Ile679del Uncertain significance ★ same residue
- DSP p.Ile679Thr Uncertain significance ★★ same residue
- DSP p.Ile679Met Conflicting classifications of pathogenicity ★ ⚠ 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
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-ile679fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown