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A586T

AlphaMissense: likely benign (0.08)Uncertain significanceTransmembrane · predicted
AlanineThreonine at position 586 · Transmembrane helix 9 · WFS1 (Wolframin)

Interactive 3D Structure

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

AlphaMissense
0.075
likely benign
AlphaFold pLDDT
79
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 conditionsAutosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram syndrome 1; Cataract 41; Wolfram-like syndrome
Population frequency (gnomAD v4)Ultra-rare · AF 0.0027%
cDNA changec.1756G>A
ClinVar accessionVCV002577827
Last evaluated2025/11/10 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

A586T — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Alanine (A) → Threonine (T) at position 586 Domain context: Transmembrane helix 9


AlphaMissense

  • Pathogenicity score: 0.0755
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 586: 79.12

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: Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram syndrome 1; Cataract 41; Wolfram-like syndrome
  • cDNA change: c.1756G>A
  • ClinVar accession: VCV002577827
  • Last evaluated: 2025/11/10 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.638437Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the A586T 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 A586T PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.