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V333I

AlphaMissense: likely benign (0.05)Likely benignTransmembrane · predicted
ValineIsoleucine at position 333 · Cytoplasmic loop 1 · WFS1 (Wolframin)

Interactive 3D Structure

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

AlphaMissense
0.046
likely benign
AlphaFold pLDDT
72
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 conditionsWFS1-Related Spectrum Disorders; Wolfram syndrome 1; Wolfram-like syndrome; Type 2 diabetes mellitus; Autosomal dominant nonsyndromic hearing loss 6; Cataract 41
Population frequency (gnomAD v4)Common · AF 74.94%
cDNA changec.997G>A
ClinVar accessionVCV000045463
Last evaluated2026/02/04 00:00

Population frequency too high for a penetrant Wolfram allele — stand-alone benign evidence (ACMG BA1).

Full Variant Card

V333I — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Valine (V) → Isoleucine (I) at position 333 Domain context: Cytoplasmic loop 1


AlphaMissense

  • Pathogenicity score: 0.0465
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 333: 71.5

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.


Clinical evidence

  • Classification: Benign/Likely benign
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: WFS1-Related Spectrum Disorders; Wolfram syndrome 1; Wolfram-like syndrome; Type 2 diabetes mellitus; Autosomal dominant nonsyndromic hearing loss 6; Cataract 41
  • cDNA change: c.997G>A
  • ClinVar accession: VCV000045463
  • Last evaluated: 2026/02/04 00:00
  • Submissions: 2

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.465645Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the V333I 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 V333I PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.