# I421V — WFS1 Molecular Atlas Card

**Variant type:** Missense
**Substitution:** Isoleucine (I) → Valine (V) at position 421
**Domain context:** Transmembrane helix 4

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## AlphaMissense

- **Pathogenicity score:** 0.0581
- **Class:** likely benign

## AlphaFold confidence

- **pLDDT at residue 421:** 84.5

> **DynaMut2 ΔΔG:** not yet computed for this variant — AlphaMissense + AlphaFold
> confidence shown above. Stability ΔΔG and the wild-type/mutant structural
> comparison backfill behind this note.

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## Clinical evidence

- **Classification:** Benign/Likely benign
- **Review status:** criteria provided, multiple submitters, no conflicts
- **Associated conditions:** Wolfram syndrome 1
- **cDNA change:** c.1261A>G
- **ClinVar accession:** VCV000166585
- **Last evaluated:** 2014/10/19 00:00
- **Submissions:** 1

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_Card generated by `wolfram-atlas-batch` (missense AlphaMissense mint) on 2026-06-08T02:27:33.524238Z._
_AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024._