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R138H

AlphaMissense: likely benign (0.18)Uncertain significanceCytoplasmic · predicted
Arginine → Histidine at position 138 · N-terminal cytoplasmic (intrinsically disordered) · WFS1 (Wolframin)

Interactive 3D Structure

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

AlphaMissense
0.178
likely benign
AlphaFold pLDDT
89
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 syndrome 1; Wolfram-like syndrome; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus
Population frequency (gnomAD v4)Ultra-rare · AF 0.0011%
cDNA changec.413G>A
ClinVar accessionVCV002073332
Last evaluated2024/06/09 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

R138H — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Arginine (R) → Histidine (H) at position 138 Domain context: N-terminal cytoplasmic (intrinsically disordered)

AlphaMissense

  • Pathogenicity score: 0.1781
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 138: 89.06

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 syndrome 1; Wolfram-like syndrome; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus
  • cDNA change: c.413G>A
  • ClinVar accession: VCV002073332
  • Last evaluated: 2024/06/09 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.370564Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the R138H 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 R138H PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.