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R375H

AlphaMissense: likely benign (0.12)Uncertain significanceTransmembrane · predicted
Arginine → Histidine at position 375 · Transmembrane helix 3 · WFS1 (Wolframin)

Interactive 3D Structure

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

AlphaMissense
0.116
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 conditionsMonogenic diabetes; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Cataract 41; Wolfram syndrome 1; Wolfram-like syndrome; Retinal dystrophy
Population frequency (gnomAD v4)Low frequency · AF 0.033%
cDNA changec.1124G>A
ClinVar accessionVCV000504709
Last evaluated2026/01/15 00:00

Observed in the general population.

Full Variant Card

R375H — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Arginine (R) → Histidine (H) at position 375 Domain context: Transmembrane helix 3

AlphaMissense

  • Pathogenicity score: 0.1162
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 375: 83.0

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: Monogenic diabetes; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Cataract 41; Wolfram syndrome 1; Wolfram-like syndrome; Retinal dystrophy
  • cDNA change: c.1124G>A
  • ClinVar accession: VCV000504709
  • Last evaluated: 2026/01/15 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.491455Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the R375H 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 R375H PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.