T600=
SynonymousSilentBenignTransmembrane · predictedSilent — Silent — no amino-acid change
Interactive 3D Structure
AlphaFold wild-type wolframin · the variant site near residue 600 (C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)) is highlighted.
Variant Assessment
Therapeutic Implication · Silent
Clinical Evidence
Observed in the general population.
ClinVar classifies this variant as Benign for WFS1-related spectrum (unresolved mode) (dominant or recessive); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). ClinVar records this under a WFS1-spectrum label that spans both disease families — recessive Wolfram syndrome (biallelic) and the dominant WFS1-related disorders. The label does not resolve which applies, and it is not a severity statement.
- WFS1-related spectrum (unresolved mode)dominant or recessivesubmitted as: WFS1-Related Spectrum Disorders
- Nonsyndromic hearing loss (DFNA6/14/38)autosomal dominant · OMIM 600965submitted as: Autosomal dominant nonsyndromic hearing loss 6
- 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 3.64% (2733 of 75,050 alleles), 16.8x the global figure. The global AF describes the general population, not the at-risk group.
55 homozygotes reported in gnomAD v4 (51 African / African American; 2 Admixed American; 1 Remaining individuals; 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. |
|---|---|---|---|---|
| African / African American | 3.64% | 2,733 / 75,050 | 51 | ~1 in 14 |
| Admixed American | 0.461% | 277 / 60,028 | 2 | ~1 in 110 |
| Remaining individuals | 0.286% | 179 / 62,508 | 1 | ~1 in 170 |
| Middle Eastern | 0.066% | 4 / 6,062 | 0 | ~1 in 760 |
| East Asian | 0.049% | 22 / 44,866 | 0 | ~1 in 1020 |
| South Asian | 0.025% | 23 / 91,084 | 1 | ~1 in 1980 |
| European (non-Finnish) | 0.022% | 265 / 1,180,028 | 0 | ~1 in 2230 |
| Finnish · under-sampled | 0.0016% | 1 / 64,004 | 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
T600= — WFS1 Molecular Atlas Card
Variant type: Synonymous (silent) Codon: position 600 (Threonine, T) — amino acid unchanged Domain context: C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)
Schema category: Silent — Silent — no amino-acid change
No amino-acid change (T600 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 — for WFS1-related spectrum (unresolved mode) (dominant or recessive); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)
ClinVar classifies this variant as Benign for WFS1-related spectrum (unresolved mode) (dominant or recessive); Nonsyndromic hearing loss (DFNA6/14/38) (autosomal dominant, OMIM 600965); Wolfram syndrome (classic) (autosomal recessive, OMIM 222300). ClinVar records this under a WFS1-spectrum label that spans both disease families — recessive Wolfram syndrome (biallelic) and the dominant WFS1-related disorders. The label does not resolve which applies, and it is not a severity statement.
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
- Review status: criteria provided, multiple submitters, no conflicts
- Associated conditions: WFS1-Related Spectrum Disorders; Autosomal dominant nonsyndromic hearing loss 6; Wolfram syndrome 1
- cDNA change: c.1800C>T
- ClinVar accession: VCV000137916
- Last evaluated: 2026/02/01 00:00
- Submissions: 1
Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:55:02.368195Z.
WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.