DSG2 p.Gly577Arg
c.1729G>C · rs2073247973 · VCV2260291
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5387 | ambiguous |
|---|---|---|
| REVEL | 0.473 | indeterminate |
| SaProt | LLR -9.90 | tolerated |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 48 kb · p 0.014 · regional, not allelic |
| Overall | ||
| CADD | 25.9 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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.Gly577Arg
- Coding
- c.1729G>C
- MANE Select
- NM_001943
- dbSNP
- rs2073247973
- Type
- single nucleotide variant
- Location
- chr18:31538828 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.27 · 12 PDB
- Residue 577
- a β-strand; 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)
Similar variants
- DSG2 p.Gly577Ala Uncertain significance ★★ ⚠ same residue
- DSG2 p.Gly577Ser Uncertain significance ★ ⚠ same residue
- DSG2 p.Gly577= Likely benign ★ same residue
- DSG2 c.1423+1G>T Likely pathogenic ★★ same condition
- DSG2 c.1424-1G>A Likely pathogenic ★★ same condition
- DSG2 c.523+1G>T Pathogenic/Likely pathogenic ★★ same condition
- DSG2 c.690+1G>A Pathogenic ★★ same condition
- DSG2 c.81+1G>T 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-gly577arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown