A58V
Category 5 — IDR ExclusionConflictingCytoplasmic · predictedEditorialAla→Val p58 IDR AM=0.09 ddg=-0.68 pLDDT=26. ClinVar Conflicting evidence. Atlas mechanism: see structural analysis.
Interactive 3D Structure
Computational Predictions
- pLDDT 26.17 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, but does not state what it is classified for. ClinVar records the condition only as "not provided". A classification without a phenotype and an inheritance mode cannot be read as a statement about Wolfram syndrome risk or severity.
- 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 East Asian: AF 0.094% (40 of 42,630 alleles), 17.8x the global figure. The global AF describes the general population, not the at-risk group.
1 homozygote reported in gnomAD v4 (1 South Asian). gnomAD excludes individuals with severe pediatric disease, so homozygotes in this dataset argue against a fully penetrant severe recessive phenotype and belong in the clinical picture. This is interpretive signal, not a classification.
| Ancestry group | Allele freq. | AC / AN | Hom. | Carrier est. |
|---|---|---|---|---|
| East Asian | 0.094% | 40 / 42,630 | 0 | ~1 in 530 |
| Remaining individuals | 0.035% | 21 / 60,852 | 0 | ~1 in 1450 |
| South Asian | 0.0082% | 7 / 85,450 | 1 | ~1 in 6100 |
| African / African American | 0.0054% | 4 / 74,094 | 0 | ~1 in 9260 |
| Admixed American · under-sampled | 0.0019% | 1 / 54,050 | 0 | — |
| European (non-Finnish) | 0.00086% | 10 / 1,158,544 | 0 | ~1 in 57930 |
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: ALA59 (2.5 Å), ALA57 (2.5 Å — partner of A57S/A57T). pLDDT 26 deep IDR. Multiple A57 substitutions Atlas-tracked. 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 A58V 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.