A43V
Category 5 — IDR ExclusionConflictingCytoplasmic · predictedEditorialAla→Val p43 IDR AM=0.08 ddg=-1.11 pLDDT=28. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.
Interactive 3D Structure
Computational Predictions
- pLDDT 28.23 below 70
The underlying AlphaFold model has pLDDT below 70 at this position, so the structure the stability calculation was run on is itself uncertain.
Do not rank this value against a variant from a different region on ΔΔG alone.
Clinical Evidence
Observed at very low frequency in gnomAD.
ClinVar classifies this variant as Conflicting classifications of pathogenicity for Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). Classic Wolfram syndrome is recessive: a single copy does not produce it, and this classification says nothing about a carrier's own risk.
- Wolfram syndrome (classic)autosomal recessive · OMIM 222300submitted as: Wolfram syndrome 1
- Submitters conflict on this classification (1★). Treat the conditions above as submitted, not as documented phenotypes.
- Phenotype scope is interpretation of submitted records. The computed values on this card (AlphaMissense, DynaMut2 ΔΔG, pLDDT) are measurements of the model, not of a patient.
- Presentation cannot be generalised from neighbouring variants: one nucleotide over can present very differently. Structural similarity supports a mechanistic hypothesis, never a phenotype claim.
Review status: 1★ conflicting classifications. ClinVar "conditions" is the union of all submissions; 0–1★ entries are submitted conditions, not documented phenotypes.
Highest in European (non-Finnish): AF 0.00055% (6 of 1,096,674 alleles), in line with the global figure.
No homozygotes reported in gnomAD v4. For a recessive allele this is expected and is not, on its own, evidence either way.
| Ancestry group | Allele freq. | AC / AN | Hom. | Carrier est. |
|---|---|---|---|---|
| European (non-Finnish) | 0.00055% | 6 / 1,096,674 | 0 | ~1 in 91390 |
Source: gnomAD r4, retrieved 2026-08-21. Values are allele frequencies. The carrier estimate is derived from the allele frequency (Hardy-Weinberg, ~2·AF) and is an approximation, not a published figure — where a published carrier frequency exists it outranks this column and is cited on the card.
Structural Context
Position analysis: ARG42 (2.5 Å — R42Q!), PRO44 (2.5 Å), PRO41 (4.9 Å). pLDDT 28 deep IDR. Substantial ΔΔG but untrustworthy. The Atlas's neighbor extraction surfaces this variant's contacts and connects them to the broader multi-variant target landscape.
Druggability Assessment
Why this matters
Feed this card to Wolfram Intelligence
Download the A43V 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.