Q584=
SynonymousSilentLikely benignTransmembrane · predictedSilent — Silent — no amino-acid change
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 584 (Transmembrane helix 9) is highlighted.
Variant Assessment
Therapeutic Implication · Silent
Clinical Evidence
Observed at very low frequency in gnomAD.
ClinVar classifies this variant as Likely benign for Wolfram-like syndrome (autosomal dominant, OMIM 614296); Cataract 41 (autosomal dominant, OMIM 116400); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related diabetes (autosomal dominant); 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.
- Wolfram-like syndromeautosomal dominant · OMIM 614296submitted as: Wolfram-like syndrome
- Cataract 41autosomal dominant · OMIM 116400submitted as: Cataract 41
- 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 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 0.025% (19 of 74,944 alleles), 11.7x 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 | 0.025% | 19 / 74,944 | 0 | ~1 in 1970 |
| European (non-Finnish) | 0.0014% | 16 / 1,180,052 | 0 | ~1 in 36880 |
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
Q584= — WFS1 Molecular Atlas Card
Variant type: Synonymous (silent) Codon: position 584 (Glutamine, Q) — amino acid unchanged Domain context: Transmembrane helix 9
Schema category: Silent — Silent — no amino-acid change
No amino-acid change (Q584 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
Likely benign — for Wolfram-like syndrome (autosomal dominant, OMIM 614296); Cataract 41 (autosomal dominant, OMIM 116400); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related diabetes (autosomal dominant); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)
ClinVar classifies this variant as Likely benign for Wolfram-like syndrome (autosomal dominant, OMIM 614296); Cataract 41 (autosomal dominant, OMIM 116400); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); WFS1-related diabetes (autosomal dominant); 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: Likely benign
- Review status: criteria provided, multiple submitters, no conflicts
- Associated conditions: Wolfram-like syndrome; Cataract 41; Autosomal dominant nonsyndromic hearing loss 6; Type 2 diabetes mellitus; Wolfram syndrome 1
- cDNA change: c.1752G>A
- ClinVar accession: VCV001562848
- Last evaluated: 2024/05/13 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:54:53.837371Z.
WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.