A43V

Category 5 — IDR ExclusionConflictingCytoplasmic · predictedEditorial

Alanine → Valine at position 43 · N-terminal intrinsically disordered region (1-86) · WFS1 (Wolframin)

Ala→Val p43 IDR AM=0.08 ddg=-1.11 pLDDT=28. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type A43 — native residue, no strong sidechain contacts

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DynaMut2 mutant · A43V

Mutant V43 — energy-minimized; local contact network preserved

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Computational Predictions

DynaMut2 ΔΔG

-1.11kcal/mol

Destabilising — moderate

AlphaMissense

0.077

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 0.00042%

cDNA changec.128C>T

ClinVar accessionVCV000166568

Last evaluated2013/11/06 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position analysis: ARG42 (2.5 Å — R42Q!), PRO44 (2.5 Å), PRO41 (4.9 Å). pLDDT 28 deep IDR. Substantial ΔΔG but untrustworthy. The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.

Amino-acid chemistry

conservative volume increase

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

Deep IDR adjacent to R42Q.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the A43V 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 A43V PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Region1–321 · Interaction with ATP6V1A

Region1–86 · Disordered