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T857I

AlphaMissense: likely benign (0.11)Uncertain significanceLumenal · predictedσ-1 candidate
ThreonineIsoleucine at position 857 · 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
0.111
likely benign
AlphaFold pLDDT
48
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 conditionsWolfram syndrome 1
Population frequency (gnomAD v4)Ultra-rare · AF 0.00056%
cDNA changec.2570C>T
ClinVar accessionVCV002442313
Last evaluated1/01/01 00:00

Observed at very low frequency in gnomAD.

Full Variant Card

T857I — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Threonine (T) → Isoleucine (I) at position 857 Domain context: C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)


AlphaMissense

  • Pathogenicity score: 0.1113
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 857: 47.78

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
  • Associated conditions: Wolfram syndrome 1
  • cDNA change: c.2570C>T
  • ClinVar accession: VCV002442313
  • Last evaluated: 1/01/01 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.820310Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the T857I 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 T857I PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.