P10S

Category 5 — IDR ExclusionConflictingCytoplasmic · predictedEditorial

Proline → Serine at position 10 · N-terminal intrinsically disordered region (1-86) · WFS1 (Wolframin)

Pro→Ser p10 IDR AM=0.06 ddg=-0.23 pLDDT=35. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type P10 — polar contact to C12

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DynaMut2 mutant · P10S

Mutant S10 — energy-minimized; local contact network preserved

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Bond changes · DynaMut2 interaction analysis

0 lost0 gained1 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Polar contact	C12	C12	Preserved

Lost / gained / preserved interatomic contacts at the variant residue, from the DynaMut2 (Arpeggio) interaction analysis of the wild-type and energy-minimized mutant structures.

Computational Predictions

DynaMut2 ΔΔG

-0.23kcal/mol

Destabilising — mild

AlphaMissense

0.064

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 0.0031%

cDNA changec.28C>T

ClinVar accessionVCV000349302

Last evaluated2024/09/11 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position analysis: SER11 (2.4 Å), GLY9 (2.5 Å). pLDDT 35 deep IDR. 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

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 proline removal.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the P10S 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 P10S PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Region1–321 · Interaction with ATP6V1A

Region1–86 · Disordered

Compositional bias10–20 · Pro residues