DSC2 p.Ser526Ter
c.1577C>A · rs887847751 · VCV1693178
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
arrhythmogenic right ventricular cardiomyopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 11 of 16 |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP -0.7, phastCons 0.39 |
| Overall | ||
| CADD | 35.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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.Ser526Ter
- Coding
- c.1577C>A
- MANE Select
- NM_024422
- dbSNP
- rs887847751
- Type
- single nucleotide variant
- Location
- chr18:31079933 (GRCh38)
- Gene constraint
- LOEUF 0.743 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 77.26 · 3 PDB
- Residue 526
- the cadherin 4 domain
Similar variants
- DSC2 p.Ser526Ala Uncertain significance ★★ ⚠ same residue
- DSC2 p.Ser526Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- DSC2 p.Ser740Ter Likely pathogenic ★★ same condition
- DSC2 p.Tyr221Ter Pathogenic/Likely pathogenic ★★ same condition
- DSC2 c.1077+2T>G Uncertain significance ★★ same condition
- DSC2 c.2251-3C>T Uncertain significance ★★ same condition
- DSC2 p.Arg357Cys Uncertain significance ★★ ⚠ same condition
- DSC2 p.Asn573Asp Uncertain significance ★★ ⚠ 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-ser526ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown