DSG2 p.Val986fs
c.2955del · rs1064794709 · VCV420800
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 2.4 | phastCons 0.99 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
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
- DSG2
- Protein
- p.Val986fs
- Coding
- c.2955del
- MANE Select
- NM_001943
- dbSNP
- rs1064794709
- Type
- Deletion
- Location
- chr18:31546340 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.27 · 12 PDB
- Residue 986
- 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.Val986Met Uncertain significance ★ ⚠ same residue
- DSG2 p.Val986= Likely benign ★ same residue
- DSG2 c.2001_2001+5del Likely pathogenic ★★ same condition
- DSG2 c.523+1_523+2del Likely pathogenic ★★ same condition
- DSG2 p.Asn462fs Pathogenic/Likely pathogenic ★★ same condition
- DSG2 p.Leu171fs Pathogenic/Likely pathogenic ★★ same condition
- DSG2 p.Phe211fs Pathogenic ★★ same condition
- DSG2 p.Thr31fs 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/dsg2-p-val986fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown