DSC3 p.Pro599=
c.1797T>C · rs1313586 · VCV1288388
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 76.6%, afr) — too common for a highly-penetrant pathogenic allele
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 -6 | GERP -4 |
| Overall | ||
| CADD | 0.032 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
76.6%
African / African-American · 57,395/74,910 alleles
Filtering AF
76.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 75.9%
Overall
36.5%
589,351/1,613,310 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 76.6% | 1 |
| East Asian | 70.2% | 1 |
| South Asian | 48.3% | 2 |
| Middle Eastern | 39.4% | 3 |
| Remaining individualsnot grpmax-eligible | 39.1% | 3 |
| Amishnot grpmax-eligible | 35% | 3 |
| Admixed American | 34.5% | 3 |
| Finnishnot grpmax-eligible | 34.3% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 32.5% | 3 |
| European (non-Finnish) | 32% | 3 |
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.Pro599=
- Coding
- c.1797T>C
- MANE Select
- NM_024422 · reported on NM_001941
- dbSNP
- rs1313586
- Type
- single nucleotide variant
- Location
- chr18:31006998 (GRCh38)
- Structure
- AlphaFold pLDDT 77.26 · 3 PDB
- Residue 599
- the cadherin 5 domain; a UniProt-annotated variant site (in arvd11; likely pathogenic; mislocalization of dsc2 to the cytoplasm within intercalated disks of the heart)
Similar variants
- DSC2 p.Pro599Ala Uncertain significance ★★ ⚠ same residue
- DSC2 p.Pro599Arg 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
- DSC2 p.Gln620Ter 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-pro599 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown