DSC3 p.Thr275=
c.825A>G · rs74539535 · VCV777284
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.03%, afr)
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 -13 | GERP -4 |
| Overall | ||
| CADD | 2.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.03%
African / African-American · 3,027/75,022 alleles
Filtering AF
3.91%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.87%
Overall
0.208%
3,353/1,614,068 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.03% | 25 |
| Remaining individualsnot grpmax-eligible | 0.25% | 401 |
| Admixed American | 0.203% | 492 |
| Middle Eastern | 0.0825% | 1,212 |
| East Asian | 0.00446% | 22,430 |
| European (non-Finnish) | 0.00331% | 30,256 |
| South Asian | 0.0022% | 45,543 |
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
- DSC3
- Protein
- p.Thr275=
- Coding
- c.825A>G
- MANE Select
- NM_024422 · reported on NM_001941
- dbSNP
- rs74539535
- Type
- single nucleotide variant
- Location
- chr18:31022453 (GRCh38)
- Structure
- AlphaFold pLDDT 77.26 · 3 PDB
- Residue 275
- a UniProt-annotated variant site (in arvd11; can be processed into a mature form but shows a higher pro-protein to mature protein ratio; only a proportion of the partly functional mutant is incorporated into the desmosomes); the cadherin 2 domain
Similar variants
- DSC2 p.Thr275Lys Uncertain significance ★★ ⚠ same residue
- DSC2 p.Thr275= Likely benign ★★ same residue
- DSC2 p.Thr275Met Conflicting classifications of pathogenicity ★ ⚠ same residue
- DSC2 c.1521-1G>A Likely pathogenic ★★ same type
- DSC2 c.1664-1G>A Likely pathogenic ★★ same type
- DSC2 c.354+2T>A Likely pathogenic ★★ same type
- DSC2 c.355-1G>A Likely pathogenic ★★ same type
- DSC2 p.Gln554Ter Pathogenic ★★ same type
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/dsc3-p-thr275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown