F585=
SynonymousSilentLikely benignTransmembrane · predictedSilent — Silent — no amino-acid change
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 585 (Transmembrane helix 9) is highlighted.
Variant Assessment
Therapeutic Implication · Silent
Clinical Evidence
Observed at very low frequency in gnomAD.
ClinVar classifies this variant as Benign/Likely benign for Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related diabetes (autosomal dominant); Wolfram-like syndrome (autosomal dominant, OMIM 614296); Cataract 41 (autosomal dominant, OMIM 116400); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). These are two clinically distinct disease families: classic Wolfram syndrome requires two affected copies, while the dominant WFS1-related disorders do not. One label covers both, and it does not tell you which applies to a given person.
- Nonsyndromic hearing loss (DFNA6/14/38)autosomal dominant · OMIM 600965submitted as: Autosomal dominant nonsyndromic hearing loss 6
- WFS1-related diabetesautosomal dominantsubmitted as: Type 2 diabetes mellitus
- Wolfram-like syndromeautosomal dominant · OMIM 614296submitted as: Wolfram-like syndrome
- Cataract 41autosomal dominant · OMIM 116400submitted as: Cataract 41
- Wolfram syndrome (classic)autosomal recessive · OMIM 222300submitted as: Wolfram syndrome 1
- 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: 2★ multiple submitters, no conflicts. ClinVar "conditions" is the union of all submissions; 0–1★ entries are submitted conditions, not documented phenotypes.
Highest in African / African American: AF 0.023% (17 of 75,056 alleles), 2.4x the global figure. The global AF describes the general population, not the at-risk group.
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. |
|---|---|---|---|---|
| African / African American | 0.023% | 17 / 75,056 | 0 | ~1 in 2210 |
| European (non-Finnish) | 0.011% | 129 / 1,180,036 | 0 | ~1 in 4570 |
| Remaining individuals | 0.0096% | 6 / 62,510 | 0 | ~1 in 5210 |
| East Asian | 0.0045% | 2 / 44,870 | 0 | ~1 in 11220 |
| South Asian · under-sampled | 0.0011% | 1 / 91,080 | 0 | — |
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.
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Full Variant Card
F585= — WFS1 Molecular Atlas Card
Variant type: Synonymous (silent) Codon: position 585 (Phenylalanine, F) — amino acid unchanged Domain context: Transmembrane helix 9
Schema category: Silent — Silent — no amino-acid change
No amino-acid change (F585 is unchanged): the codon is altered but the protein sequence is identical to wild-type. No structural, stability or AlphaMissense effect applies. Synonymous variants are typically benign unless they affect splicing or regulatory elements; this one is not adjacent to an exon boundary.
Clinical evidence
Inheritance and scope
Benign/Likely benign — for Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related diabetes (autosomal dominant); Wolfram-like syndrome (autosomal dominant, OMIM 614296); Cataract 41 (autosomal dominant, OMIM 116400); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)
ClinVar classifies this variant as Benign/Likely benign for Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related diabetes (autosomal dominant); Wolfram-like syndrome (autosomal dominant, OMIM 614296); Cataract 41 (autosomal dominant, OMIM 116400); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). These are two clinically distinct disease families: classic Wolfram syndrome requires two affected copies, while the dominant WFS1-related disorders do not. One label covers both, and it does not tell you which applies to a given person.
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.
- Classification: Benign/Likely benign
- Review status: criteria provided, multiple submitters, no conflicts
- Associated conditions: Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram-like syndrome; Cataract 41; Wolfram syndrome 1
- cDNA change: c.1755C>T
- ClinVar accession: VCV000718145
- Last evaluated: 2026/01/17 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:54:54.909793Z.
WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.