DSG2 p.Asp846fs
c.2532_2535dup · VCV4535228
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (15 of 15) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- DSG2
- Protein
- p.Asp846fs
- Coding
- c.2532_2535dup
- MANE Select
- NM_001943
- Type
- Duplication
- Location
- chr18:31545916 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.27 · 12 PDB
- Residue 846
- a UniProt-annotated variant site (in arvd10; uncertain significance; evidence of residual myocardium, fibrous tissue, fatty tissue, dysmetric and dysmorphic nuclei and prominent cytoplasmic vacuolization; decreases the number of desmosomes at intercalated disks also increases desmosome gap; smaller intercellular gaps, with repeating couplings, abnormally located desmosomes and pale internal plaques); a UniProt-annotated variant site (in arvd10; uncertain significance)
Similar variants
- DSG2 p.Asp846Tyr Uncertain significance ★★ ⚠ same residue
- DSG2 p.Asp846= Likely benign ★★ same residue
- DSG2 p.Leu610fs Pathogenic/Likely pathogenic ★★ same type
- DSG2 p.Thr291fs Pathogenic ★★ same type
- DSG2 p.Val271fs Pathogenic/Likely pathogenic ★★ same type
- DSG2 p.Gln1114_His1115insGln Uncertain significance ★★ same type
- DSG2 p.Glu1048_Pro1053dup Uncertain significance ★★ same type
- DSG2 p.Pro958delinsGlnGlnLysLeuProMetSerGlnGlyProLeuCysHisGlnProLeuTer Uncertain significance ★★ same type
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/dsg2-p-asp846fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown