DSG2 p.Cys637=
c.1911C>T · rs201654341 · VCV44292
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 14 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.94%, sas)
Conditions
3
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.98 | GERP -2, phastCons 0.005 |
| Overall | ||
| CADD | 4.377 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.94%
South Asian · 1,768/91,086 alleles
Filtering AF
1.87%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.84%
Overall
0.117%
1,885/1,614,118 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.94% | 52 |
| Remaining individualsnot grpmax-eligible | 0.107% | 933 |
| Middle Eastern | 0.033% | 3,029 |
| East Asian | 0.0223% | 4,489 |
| African / African-American | 0.00666% | 15,006 |
| Admixed American | 0.00333% | 30,013 |
| European (non-Finnish) | 0.00254% | 39,333 |
| Finnishnot grpmax-eligible | 0.00156% | 64,004 |
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.Cys637=
- Coding
- c.1911C>T
- MANE Select
- NM_001943
- dbSNP
- rs201654341
- Type
- single nucleotide variant
- Location
- chr18:31541224 (GRCh38)
- Gene constraint
- LOEUF 0.764 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.27 · 12 PDB
- Residue 637
- 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 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
- DSG2 p.Arg46Trp 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-cys637 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown