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Q667=

SynonymousSilentBenignLumenal · predicted
Synonymous variant · codon at position 667 · C-terminal ER-lumenal (calcium binding, calmodulin, chaperone) · WFS1 (Wolframin)

Silent — Silent — no amino-acid change

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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AlphaFold wild-type wolframin · the variant site near residue 667 (C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)) is highlighted.

Variant Assessment

Variant type
Synonymous
Schema
Silent
Silent — no amino-acid change
Domain
C-terminal ER-lumenal (calcium binding, calmodulin, chaperone)
Status
—

Therapeutic Implication · Silent

No amino-acid change (Q667 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

ClinVar classificationBenign
Review statuscriteria provided, single submitter
Associated conditionsWolfram syndrome 1
Population frequency (gnomAD v4)Ultra-rare · AF 0.00062%
cDNA changec.2001G>A
Protein consequenceQ667=
ClinVar variantNM_006005.3(WFS1):c.2001G>A (p.Gln667=)
ClinVar accessionVCV002429475
Last evaluated1/01/01 00:00

Observed at very low frequency in gnomAD.

Classified for1★ unverified submission

ClinVar classifies this variant as Benign 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
  • This rests on a single submitter (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★ single submitter. ClinVar "conditions" is the union of all submissions; 0–1★ entries are submitted conditions, not documented phenotypes.

Population frequency
Global (all ancestries)
AF 0.00062% · 9 / 1,461,000 alleles
Homozygotes
0
Highest-frequency population
South Asian · AF 0.0093%

Highest in South Asian: AF 0.0093% (8 of 86,258 alleles), 15.1x 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 groupAllele freq.AC / ANHom.Carrier est.
South Asian0.0093%8 / 86,2580~1 in 5390
Remaining individuals · under-sampled0.0017%1 / 60,3840—

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.

Therapeutic Strategy Handoff · prediction

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Full Variant Card

Q667= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 667 (Glutamine, Q) — 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 (Q667 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 Wolfram syndrome (classic) (autosomal recessive, OMIM 222300)

ClinVar classifies this variant as Benign 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.

This rests on a single submitter (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.

  • Classification: Benign
  • Review status: criteria provided, single submitter
  • Associated conditions: Wolfram syndrome 1
  • cDNA change: c.2001G>A
  • ClinVar accession: VCV002429475
  • Last evaluated: 1/01/01 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:55:28.892281Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.