DSG2 p.Ser194=
c.582G>A · rs748768578 · VCV928238
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
Conditions
3
arrhythmogenic right ventricular cardiomyopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.35 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -3.9, phastCons 0.003 |
| Overall | ||
| CADD | 13.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,060 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00143%
23/1,613,710 alleles · very rare
exomes 22/1,461,570 · genomes 1/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,765 |
| Admixed American | 0.00167% | 59,996 |
| European (non-Finnish) | 0.00144% | 69,402 |
| African / African-American | 0.00134% | 74,904 |
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.Ser194=
- Coding
- c.582G>A
- MANE Select
- NM_001943
- dbSNP
- rs748768578
- Type
- single nucleotide variant
- Location
- chr18:31522141 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.27 · 12 PDB
- Residue 194
- a UniProt-annotated variant site (in arvd10; uncertain significance; partial myocyte loss with fibrosis replacement in the right ventricular endomyocardium; disorganization of the intercalated disk, irregularly orientated smaller desmosome junctions with wider intercellular junction gap; significant decrease in protein abundance of dsg2 and gja1 in both the cytoplasm and cell junctions; accumulation of dsg2 and gja1 in the perinuclear region); the cadherin 2 domain; a turn
Similar variants
- DSG2 p.Ser194Leu Conflicting classifications of pathogenicity ★ ⚠ 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
- DSG2 c.829-2A>T Likely pathogenic ★★ same condition
- DSG2 p.Arg46Gln 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-ser194 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown