# c.1525_1539del — WFS1 Molecular Atlas Card

**Variant type:** In-frame indel
**Change:** 5 residue(s) deleted in frame at position 509
**Domain context:** Transmembrane helix 7

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## Schema category: **I3 — Multi-residue in-frame indel — likely major structural disruption**

5 residues removed in frame around position 509 (Transmembrane helix 7). A change this size usually perturbs local packing and can propagate to the fold. Gene therapy is the primary path unless an AlphaFold prediction of the modified sequence shows a surprisingly intact fold. Predicted structure pending (ColabFold).

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## Structural prediction

- **Reading frame:** preserved (in-frame) — no premature stop, NMD does not apply.
- **Affected domain:** Transmembrane helix 7
- **Predicted modified structure:** _pending — AlphaFold/ColabFold prediction of the
  modified sequence and backbone-RMSD vs wild-type backfill here (Wave 2)._

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## Clinical evidence

- **Classification:** Pathogenic/Likely pathogenic
- **Review status:** criteria provided, multiple submitters, no conflicts
- **Associated conditions:** Autosomal dominant nonsyndromic hearing loss 6; Wolfram syndrome 1; Type 2 diabetes mellitus; Wolfram-like syndrome; Cataract 41
- **cDNA change:** c.1525_1539del
- **ClinVar accession:** VCV001453842
- **Last evaluated:** 2024/09/22 00:00
- **Submissions:** 1

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_Card generated by `wolfram-atlas-batch` (in-frame indel pipeline) on 2026-06-08T02:41:21.492262Z._
_Schema: `reference/card_schema_extension.md` (I1–I3). WFS1: UniProt O76024, AlphaFold v6._