# c.1401_1403del — WFS1 Molecular Atlas Card

**Variant type:** In-frame indel
**Change:** 1 residue(s) deleted in frame at position 467
**Domain context:** Transmembrane helix 6

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

A single residue removed inside Transmembrane helix 6 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 6
- **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:** Wolfram syndrome 1
- **cDNA change:** c.1401_1403del
- **ClinVar accession:** VCV001070757
- **Last evaluated:** 2025/01/26 00:00
- **Submissions:** 1

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_Card generated by `wolfram-atlas-batch` (in-frame indel pipeline) on 2026-06-08T02:41:11.860074Z._
_Schema: `reference/card_schema_extension.md` (I1–I3). WFS1: UniProt O76024, AlphaFold v6._