V624A

Category 5 — IDR ExclusionConflictingTransmembrane · predictedEditorial

Valine → Alanine at position 624 · Connecting loop · WFS1 (Wolframin)

Valine → Alanine at position 624 in connecting loop. ClinVar Conflicting including WFS1 spectrum. AlphaMissense 0.16 (below threshold) — AM under-call. DynaMut2 ΔΔG +0.13 (neutral). pLDDT 47 — IDR boundary.

Interactive 3D Structure

Wild-type reference

Wild-type V624 — hydrogen bond to T628

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DynaMut2 mutant · V624A

Mutant A624 — hydrogen bond to V620 lost (2 contacts lost)

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Bond changes · DynaMut2 interaction analysis

2 lost1 gained8 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	V620	V620	Preserved
Hydrogen bond	—	V621	Gained
Hydrogen bond	L627	L627	Preserved
Hydrogen bond	T628	T628	Preserved
Polar contact	V620	V620	Preserved
Polar contact	V621	V621	Preserved
Polar contact	S626	—	Lost
Polar contact	L627	L627	Preserved
Polar contact	T628	T628	Preserved
Van der Waals	S626	S626	Preserved
Van der Waals	L627	—	Lost

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

0.13kcal/mol

Stabilising — mild

AlphaMissense

0.160

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 conditionsWFS1-Related Spectrum Disorders

InheritanceWFS1 spectrum.

Population frequency (gnomAD v4)Ultra-rare · AF 0.0013%

cDNA changec.1871T>C

ClinVar accessionVCV000289011

Last evaluated2025/11/28 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position 624 at pLDDT 47 — BELOW the 50 threshold for trustworthy structure. Neighbors: MET623 (2.5 Å), LYS625 (2.5 Å), VAL621 (3.8 Å).

V624A conservative volume reduction in a disordered region. Computational predictions deserve caution. AM 0.16 under-call; WFS1 spectrum documented.

Amino-acid chemistry

Valine (V) → Alanine (A) — branched aliphatic replaced by small methyl. Volume reduction.

Position in the protein

Connecting loop · position 624 (pLDDT 47 — IDR boundary).

Druggability Assessment

Category 5 — IDR Exclusion. pLDDT 47 below the 50 threshold. AlphaMissense 0.16 below threshold. DynaMut2 prediction not trustworthy.

The Atlas routes Category 5 variants to wet-lab characterization rather than computational drug discovery.

Why this matters

V624A is another IDR-boundary variant — Atlas appropriately flags.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the V624A 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 V624A PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin