# c.2455_2502del — WFS1 Molecular Atlas Card

**Variant type:** In-frame indel
**Change:** 16 residue(s) deleted in frame at position 819
**Domain context:** C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)

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

16 residues removed in frame around position 819 (C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)). 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:** C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)
- **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:** Conflicting classifications of pathogenicity
- **Review status:** criteria provided, conflicting classifications
- **Associated conditions:** Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram syndrome 1; Cataract 41; Wolfram-like syndrome
- **cDNA change:** c.2455_2502del
- **ClinVar accession:** VCV001958301
- **Last evaluated:** 2025/10/03 00:00
- **Submissions:** 1

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_Card generated by `wolfram-atlas-batch` (in-frame indel pipeline) on 2026-06-08T02:41:50.637086Z._
_Schema: `reference/card_schema_extension.md` (I1–I3). WFS1: UniProt O76024, AlphaFold v6._