R629Q

Category 4 — Stable Fold, Function DisruptedConflictingTransmembrane · predictedEditorial

Arginine → Glutamine at position 629 · Connecting loop · WFS1 (Wolframin)

Arg→Gln p629 loop AM=0.09 ddg=-0.63 pLDDT=60. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.

Interactive 3D Structure

Wild-type reference

Wild-type R629 — hydrogen bond to S626

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DynaMut2 mutant · R629Q

Mutant Q629 — polar contact contact to S631 lost

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Bond changes · DynaMut2 interaction analysis

1 lost0 gained7 preserved

Interaction type	Wild-type partner	Mutant partner	Status
Hydrogen bond	S626	S626	Preserved
Hydrogen bond	M632	M632	Preserved
Polar contact	S626	S626	Preserved
Polar contact	L627	L627	Preserved
Polar contact	S631	S631	Preserved
Polar contact	M632	M632	Preserved
Van der Waals	L627	L627	Preserved
Van der Waals	S631	—	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

-0.63kcal/mol

Destabilising — mild

AlphaMissense

0.092

LBen

AlphaFold pLDDT

model confidence

Schema

Cat 4

Category 4 — Stable Fold, Function Disrupted

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 0.0030%

cDNA changec.1886G>A

ClinVar accessionVCV000045443

Last evaluated2025/06/12 00:00

Observed at very low frequency in gnomAD.

Structural Context

Position analysis: THR628 (2.5 Å — same R629 microregion as R629W), SER630 (2.5 Å), SER626 (3.8 Å). Same position as R629W (AM under-call sister). The Atlas's neighbor extraction surfaces this variant's contacts.

Amino-acid chemistry

charge loss, amide preserved

Position in the protein

Connecting loop

Druggability Assessment

Cat 3/4 AM under-call — see structural prose. AlphaMissense below threshold (AM under-call class) but mechanism is structurally clear from neighbor analysis. Therapeutic strategy: site-directed at the contacts identified above.

Why this matters

R629W + R629Q sister variants.

Therapeutic Strategy Handoff · prediction

Feed this card to Wolfram Intelligence

Download the R629Q 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 R629Q PDF card ↓Strategies are AI-generated predictions, not validated therapeutics.

UniProt Domain Annotation

Chain1–890 · Wolframin

Natural variant629–629 · in WFS1; dbSNP:rs71530910