DSC2 p.Leu20=
c.60G>A · rs1201166808 · VCV1172208
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000787%, nfe)
Conditions
4
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 4.4 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 14.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000787%
European (non-Finnish) · 9/1,144,136 alleles
Filtering AF
0.00037%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000268%
Overall
0.000588%
9/1,531,278 alleles · very rare
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
- DSC2
- Protein
- p.Leu20=
- Coding
- c.60G>A
- MANE Select
- NM_024422
- dbSNP
- rs1201166808
- Type
- single nucleotide variant
- Location
- chr18:31101912 (GRCh38)
- Gene constraint
- LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.26 · 3 PDB
Similar variants
- DSC2 p.Leu20Arg Uncertain significance ★ ⚠ same residue
- DSC2 c.1521-1G>A Likely pathogenic ★★ same condition
- DSC2 c.1664-1G>A Likely pathogenic ★★ same condition
- DSC2 c.354+2T>A Likely pathogenic ★★ same condition
- DSC2 c.355-1G>A Likely pathogenic ★★ same condition
- DSC2 p.Gln554Ter Pathogenic ★★ same condition
- DSC2 p.Gln620Ter Pathogenic ★★ same condition
- DSC2 p.Glu127Ter 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/dsc2-p-leu20 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown