DSC2 p.Cys341Tyr
c.1022G>A · VCV4690014
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9767 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9767 | likely pathogenic · top 5% in DSC2 |
|---|---|---|
| REVEL | 0.248 | benign-leaning |
| SaProt | LLR -10.82 | damaging |
| ⇒ AlphaMissense and SaProt call this damaging; REVEL does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 0.8, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 34 kb · p 0.48 · regional, not allelic |
| Overall | ||
| CADD | 26.1 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- DSC2
- Protein
- p.Cys341Tyr
- Coding
- c.1022G>A
- MANE Select
- NM_024422
- Type
- single nucleotide variant
- Location
- chr18:31082981 (GRCh38)
- Gene constraint
- LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.26 · 3 PDB
- Residue 341
- a β-strand; the cadherin 2 domain
Similar variants
- DSC2 p.Cys341Phe Uncertain significance ★ ⚠ same residue
- DSC3 p.Cys341Ser Uncertain significance ★ ⚠ 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/dsc2-p-cys341tyr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown