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I720V

AlphaMissense: likely benign (0.07)Likely benignLumenal · predictedσ-1 candidate
Isoleucine → Valine at position 720 · C-terminal ER-lumenal (calcium binding, calmodulin, chaperone) · WFS1 (Wolframin)

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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Computational Predictions

AlphaMissense
0.069
likely benign
AlphaFold pLDDT
85
model confidence
DynaMut2 ΔΔG
pending
not yet computed
ClinVar
Likely benign
Benign/Likely benign

AlphaMissense + AlphaFold card. This variant is mapped from AlphaMissense pathogenicity and AlphaFold confidence. The DynaMut2 ΔΔG stability prediction and the wild-type/mutant structural comparison (dual-pane + bond network) are computed per-variant and backfill here — they require a DynaMut2 submission, unlike the precomputed AlphaMissense score.

Clinical Evidence

ClinVar classificationBenign/Likely benign
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditionsMonogenic diabetes; Diabetes mellitus; WFS1-Related Spectrum Disorders; Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome
Population frequency (gnomAD v4)Low frequency · AF 0.368%
cDNA changec.2158A>G
ClinVar accessionVCV000137919
Last evaluated2026/02/01 00:00

Observed in the general population.

Full Variant Card

I720V — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Isoleucine (I) → Valine (V) at position 720 Domain context: C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)

AlphaMissense

  • Pathogenicity score: 0.0687
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 720: 84.69

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.

Clinical evidence

  • Classification: Benign/Likely benign
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: Monogenic diabetes; Diabetes mellitus; WFS1-Related Spectrum Disorders; Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome
  • cDNA change: c.2158A>G
  • ClinVar accession: VCV000137919
  • Last evaluated: 2026/02/01 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.725652Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the I720V PDF below and upload it to Wolfram Intelligence to generate therapeutic-strategy proposals — guanidinium mimetics, sigma-1 agonist docking, NAC thiol-capping. NAC is already on the bench-testing list.

Download I720V PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.