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V493A

AlphaMissense: likely benign (0.14)Uncertain significanceTransmembrane · predicted
ValineAlanine at position 493 · Lumenal loop 3 · WFS1 (Wolframin)

Interactive 3D Structure

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

AlphaMissense
0.137
likely benign
AlphaFold pLDDT
81
model confidence
DynaMut2 ΔΔG
pending
not yet computed
ClinVar
Uncertain significance
Uncertain significance

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 classificationUncertain significance
Review statuscriteria provided, multiple submitters, no conflicts
Associated conditionsInborn genetic diseases; Wolfram-like syndrome; Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus
Population frequency (gnomAD v4)Ultra-rare · AF 0.0015%
cDNA changec.1478T>C
ClinVar accessionVCV001331576
Last evaluated2026/01/26 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

V493A — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Valine (V) → Alanine (A) at position 493 Domain context: Lumenal loop 3


AlphaMissense

  • Pathogenicity score: 0.137
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 493: 80.88

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: Uncertain significance
  • Review status: criteria provided, multiple submitters, no conflicts
  • Associated conditions: Inborn genetic diseases; Wolfram-like syndrome; Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus
  • cDNA change: c.1478T>C
  • ClinVar accession: VCV001331576
  • Last evaluated: 2026/01/26 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.574476Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the V493A 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 V493A PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.