# c.1699_1704del — WFS1 Molecular Atlas Card

**Variant type:** In-frame indel
**Change:** 2 residue(s) deleted in frame at position 567
**Domain context:** Lumenal loop 4

---

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

2 residues removed in frame around position 567 (Lumenal loop 4). 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).

---

## Structural prediction

- **Reading frame:** preserved (in-frame) — no premature stop, NMD does not apply.
- **Affected domain:** Lumenal loop 4
- **Predicted modified structure:** _pending — AlphaFold/ColabFold prediction of the
  modified sequence and backbone-RMSD vs wild-type backfill here (Wave 2)._

---

## Clinical evidence

- **Classification:** Likely pathogenic
- **Review status:** criteria provided, multiple submitters, no conflicts
- **Associated conditions:** Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Cataract 41; Wolfram syndrome 1; Wolfram-like syndrome
- **cDNA change:** c.1699_1704del
- **ClinVar accession:** VCV002502815
- **Last evaluated:** 2024/07/16 00:00
- **Submissions:** 1

---

_Card generated by `wolfram-atlas-batch` (in-frame indel pipeline) on 2026-06-08T02:41:31.231295Z._
_Schema: `reference/card_schema_extension.md` (I1–I3). WFS1: UniProt O76024, AlphaFold v6._