P52T

Category 5 — IDR ExclusionConflictingCytoplasmic · predictedEditorial

Proline → Threonine at position 52 · N-terminal intrinsically disordered region (1-86) · WFS1 (Wolframin)

Pro→Thr p52 IDR AM=0.07 ddg=-0.24 pLDDT=44. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type P52 — native residue, no strong sidechain contacts

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DynaMut2 mutant · P52T

Mutant T52 — energy-minimized; local contact network preserved

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Computational Predictions

DynaMut2 ΔΔG

-0.24kcal/mol

Destabilising — 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 0.0089%

cDNA changec.154C>A

ClinVar accessionVCV000593883

Last evaluated2026/02/17 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position analysis: GLY53 (2.5 Å), GLY51 (2.5 Å — Gly-Pro-Gly motif!). pLDDT 44 IDR boundary. Sparse neighbors. The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.

Amino-acid chemistry

proline removal

Position in the protein

N-terminal IDR boundary

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

IDR-boundary proline-removal.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the P52T 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 P52T PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Region1–321 · Interaction with ATP6V1A

Region1–86 · Disordered