G76V

Category 5 — IDR ExclusionConflictingCytoplasmic · predictedEditorial

Glycine → Valine at position 76 · N-terminal intrinsically disordered region (1-86) · WFS1 (Wolframin)

Gly→Val p76 IDR AM=0.08 ddg=-1.11 pLDDT=26. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type G76 — hydrogen bond to A74

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DynaMut2 mutant · G76V

Mutant V76 — hydrogen bond contact to A74 lost

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Bond changes · DynaMut2 interaction analysis

1 lost1 gained2 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	A74	A74	Preserved
Polar contact	A74	A74	Preserved
Van der Waals	A74	—	Lost
Hydrophobic	—	A74	Gained

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

-1.11kcal/mol

Destabilising — moderate

AlphaMissense

0.084

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)Low frequency · AF 0.035%

cDNA changec.227G>T

ClinVar accessionVCV000215375

Last evaluated2026/01/05 00:00

Observed in the general population.

Structural Context

Position analysis: THR77 (2.4 Å), ASP75 (2.5 Å), ALA74 (4.3 Å). pLDDT 26 deep IDR. Substantial ΔΔG but untrustworthy in this region. The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.

Amino-acid chemistry

glycine flexibility lost

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 glycine removal.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the G76V 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 G76V PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Region1–321 · Interaction with ATP6V1A

Region1–86 · Disordered