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M312V

AlphaMissense: likely benign (0.10)Uncertain significanceTransmembrane · predicted
Methionine → Valine at position 312 · Transmembrane helix 1 · WFS1 (Wolframin)

Interactive 3D Structure

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

AlphaMissense
0.096
likely benign
AlphaFold pLDDT
58
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 conditionsCataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome
Population frequency (gnomAD v4)Ultra-rare · AF 0.000068%
cDNA changec.934A>G
ClinVar accessionVCV001429760
Last evaluated2025/10/08 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

M312V — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Methionine (M) → Valine (V) at position 312 Domain context: Transmembrane helix 1

AlphaMissense

  • Pathogenicity score: 0.0961
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 312: 57.94

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: Cataract 41; Wolfram syndrome 1; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome
  • cDNA change: c.934A>G
  • ClinVar accession: VCV001429760
  • Last evaluated: 2025/10/08 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.451055Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the M312V 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 M312V PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.