A57T

Category 5 — IDR ExclusionConflictingCytoplasmic · predictedEditorial

Alanine → Threonine at position 57 · N-terminal intrinsically disordered region (1-86) · WFS1 (Wolframin)

Ala→Thr p57 IDR AM=0.07 ddg=+0.07 pLDDT=27. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type A57 — native residue, no strong sidechain contacts

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DynaMut2 mutant · A57T

Mutant T57 — energy-minimized; local contact network preserved

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Computational Predictions

DynaMut2 ΔΔG

0.07kcal/mol

Stabilising — mild

AlphaMissense

0.068

LBen

AlphaFold pLDDT

model confidence

Schema

Cat 5

Category 5 — IDR Exclusion

Clinical Evidence

ClinVar classificationConflicting classifications of pathogenicity

Review statuscriteria provided, conflicting classifications

Associated conditions(no specific conditions catalogued)

InheritanceConflicting ClinVar classifications.

Population frequency (gnomAD v4)Ultra-rare · AF 0.0021%

cDNA changec.169G>A

ClinVar accessionVCV000252656

Last evaluated2025/12/10 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position analysis: ALA58 (2.4 Å), ASP56 (2.5 Å). pLDDT 27 deep IDR. THIRD substitution at position 57 (A57S, A57T). The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.

Amino-acid chemistry

polarity into IDR

Position in the protein

N-terminal IDR

Druggability Assessment

Cat 5 IDR — see structural prose. AlphaMissense below threshold (AM under-call class) but mechanism is structurally identified. Therapeutic strategy: site-directed at contacts identified above, or wet-lab validation if pLDDT borderline/below 50.

Why this matters

Position 57 IDR three-substitution cluster.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the A57T 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 A57T PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Region1–321 · Interaction with ATP6V1A

Region1–86 · Disordered