DSC3 p.Lys324=
c.972A>G · rs145101142 · VCV3040227
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.313%, afr)
Conditions
1
DSC3-related disorder
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 6.1 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 11.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.313%
African / African-American · 235/75,048 alleles
Filtering AF
0.28%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.267%
Overall
0.0157%
253/1,613,852 alleles · rare
exomes 120/1,461,508 · genomes 133/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.313% | 319 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,249 |
| Admixed American | 0.00833% | 12,003 |
| South Asian | 0.0022% | 45,541 |
| European (non-Finnish) | 8.48e-05% | 1,179,935 |
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.Lys324=
- Coding
- c.972A>G
- MANE Select
- NM_001941
- dbSNP
- rs145101142
- Type
- single nucleotide variant
- Location
- chr18:31018771 (GRCh38)
- Gene constraint
- LOEUF 1.271 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.53
- Residue 324
- the cadherin 2 domain
Disease context
DSC3-related disorder
Similar variants
- DSC3 p.Arg199Trp Benign ⚠ same condition
- DSC3 p.Asn491= Likely benign same condition
- DSC3 p.Glu536= Likely benign same condition
- DSC3 c.2236-2A>G Likely pathogenic ★★ same type
- DSC3 p.Arg634Cys Uncertain significance ★★ ⚠ same type
- DSC3 c.1263+106A>G Benign ★★ same type
- DSC3 c.1264-46G>A Benign ★★ same type
- DSC3 c.155-1= Benign ★★ 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-lys324 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown