RareResearch.AI
← Back to atlas

V491M

AlphaMissense: likely benign (0.10)Uncertain significanceTransmembrane · predicted
Valine → Methionine at position 491 · Lumenal loop 3 · WFS1 (Wolframin)

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
Fullscreen ↗

Computational Predictions

AlphaMissense
0.099
likely benign
AlphaFold pLDDT
83
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; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome; Wolfram syndrome 1
Population frequency (gnomAD v4)Ultra-rare · AF 0.0029%
cDNA changec.1471G>A
ClinVar accessionVCV001402442
Last evaluated2025/08/04 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

V491M — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Valine (V) → Methionine (M) at position 491 Domain context: Lumenal loop 3

AlphaMissense

  • Pathogenicity score: 0.0985
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 491: 82.88

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; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome; Wolfram syndrome 1
  • cDNA change: c.1471G>A
  • ClinVar accession: VCV001402442
  • Last evaluated: 2025/08/04 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.573211Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the V491M 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 V491M PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.