# c.1243_1245del — WFS1 Molecular Atlas Card

**Variant type:** In-frame indel
**Change:** 1 residue(s) deleted in frame at position 415
**Domain context:** Transmembrane helix 4

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## Schema category: **I1 — Single-residue deletion in a transmembrane helix — likely catastrophic kink**

A single residue removed inside Transmembrane helix 4 shifts the helical register, which typically kinks or unwinds the helix and disrupts membrane insertion — structurally similar to a severe TM missense. Gene therapy track. 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 4
- **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
- **Review status:** criteria provided, multiple submitters, no conflicts
- **Associated conditions:** WFS1-Related Spectrum Disorders; Early-onset non-syndromic cataract; Rare genetic deafness; Wolfram-like syndrome; Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus
- **cDNA change:** c.1243_1245del
- **ClinVar accession:** VCV000215406
- **Last evaluated:** 2026/01/25 00:00
- **Submissions:** 1

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_Card generated by `wolfram-atlas-batch` (in-frame indel pipeline) on 2026-06-08T02:41:02.167061Z._
_Schema: `reference/card_schema_extension.md` (I1–I3). WFS1: UniProt O76024, AlphaFold v6._