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T628M

AlphaMissense: likely benign (0.17)Uncertain significanceTransmembrane · predicted
ThreonineMethionine at position 628 · 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
0.169
likely benign
AlphaFold pLDDT
51
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 conditionsWFS1-related disorder; Inborn genetic diseases; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome; Wolfram syndrome 1
Population frequency (gnomAD v4)Low frequency · AF 0.013%
cDNA changec.1883C>T
ClinVar accessionVCV001401302
Last evaluated2025/09/07 00:00

Observed in the general population.

Full Variant Card

T628M — WFS1 Molecular Atlas Card

Variant type: Missense Substitution: Threonine (T) → Methionine (M) at position 628 Domain context: C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)


AlphaMissense

  • Pathogenicity score: 0.169
  • Class: likely benign

AlphaFold confidence

  • pLDDT at residue 628: 50.56

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: WFS1-related disorder; Inborn genetic diseases; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome; Wolfram syndrome 1
  • cDNA change: c.1883C>T
  • ClinVar accession: VCV001401302
  • Last evaluated: 2025/09/07 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (missense AlphaMissense mint) on 2026-06-08T02:27:33.670129Z. AlphaMissense (Cheng et al. 2023) · AlphaFold model v6 · UniProt O76024.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the T628M 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 T628M PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.