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R859L

AlphaMissense: likely benign (0.33)Uncertain significanceLumenal · predictedσ-1 candidate
ArginineLeucine at position 859 · C-terminal ER-lumenal (calcium binding, calmodulin, chaperone) · WFS1 (Wolframin)

Interactive 3D Structure

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

AlphaMissense
0.330
likely benign
AlphaFold pLDDT
56
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, single submitter
Associated conditions
Population frequency (gnomAD v4)Ultra-rare · AF 0.00025%
cDNA changec.2576G>T
ClinVar accessionVCV000809619
Last evaluated2019/04/01 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

R859L — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Arginine (R) → Leucine (L) at position 859 Domain context: C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)


AlphaMissense

  • Pathogenicity score: 0.3298
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 859: 55.84

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, single submitter
  • cDNA change: c.2576G>T
  • ClinVar accession: VCV000809619
  • Last evaluated: 2019/04/01 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.822770Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the R859L 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 R859L PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.