DSG2 p.Ser999Pro
c.2995T>C · VCV4015020
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0537 | likely benign |
|---|---|---|
| REVEL | 0.096 | moderately benign-leaning |
| SaProt | LLR -7.00 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.1 | |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 48 kb · p 0.014 · regional, not allelic |
| Overall | ||
| CADD | 0.116 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,251 |
| Finnishnot grpmax-eligible | 0.00156% | 64,024 |
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
- DSG2
- Protein
- p.Ser999Pro
- Coding
- c.2995T>C
- MANE Select
- NM_001943
- Type
- single nucleotide variant
- Location
- chr18:31546381 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.27 · 12 PDB
- Residue 999
- 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.Ser999Leu Uncertain significance ★★ ⚠ same residue
- DSG2 p.Ser999= Likely benign ★★ same residue
- DSG2 p.Ser999Ala Uncertain significance ★ ⚠ same residue
- DSG2 p.Ser999Trp Uncertain significance ★ ⚠ same residue
- DSG2 p.Arg46Gln Pathogenic/Likely pathogenic ★★ same condition
- DSG2 p.Arg46Trp Pathogenic/Likely pathogenic ★★ same condition
- DSG2 p.Asn266Ser Likely pathogenic ★★ same condition
- DSG2 p.Gln873Ter 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-ser999pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown