A326V
Category 4 — Stable Fold, Function DisruptedConflictingTransmembrane · predictedEditorialAlanine → Valine at position 326 inside TM1. ClinVar Conflicting for Wolfram syndrome 1. AlphaMissense 0.29 (below threshold) — AM under-call. DynaMut2 ΔΔG -0.03 kcal/mol (neutral). Third Atlas substitution at position 326 (with A326E, A326T).
Interactive 3D Structure
Bond changes · DynaMut2 interaction analysis
| Interaction type | Wild-type partner | Mutant partner | Status |
|---|---|---|---|
| Hydrogen bond | H322 | H322 | Preserved |
| Hydrogen bond | H323 | H323 | Preserved |
| Hydrogen bond | F329 | F329 | Preserved |
| Hydrogen bond | F330 | F330 | Preserved |
| Polar contact | H322 | H322 | Preserved |
| Polar contact | H323 | H323 | Preserved |
| Polar contact | I324 | I324 | Preserved |
| Polar contact | F329 | F329 | Preserved |
| Polar contact | F330 | F330 | Preserved |
| Van der Waals | I324 | I324 | Preserved |
| Hydrophobic | F330 | F330 | 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
Clinical Evidence
Observed at very low frequency in gnomAD.
Structural Context
Position 326 same neighbors as A326E/A326T: ASN325 (2.5 Å), LEU327 (2.5 Å), HIS322 (3.6 Å — H323R neighbor cluster). The H322-H323-A326 microregion is a multi-variant hub in TM1.
A326V is the most conservative substitution at position 326 (with A326E charge introduction and A326T polar introduction). All three pathogenic — position 326 is structurally inflexible regardless of substitution chemistry.
Druggability Assessment
Therapeutic strategy: same TM1 H322-H323-A326 microregion as A326E, A326T, H323R.
Why this matters
Feed this card to Wolfram Intelligence
Download the A326V 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.