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P279=

SynonymousSilentUncertain significanceCytoplasmic · predicted
Synonymous variant · codon at position 279 · N-terminal cytoplasmic (intrinsically disordered) · WFS1 (Wolframin)

Silent — Silent — but near an exon boundary (splice effect possible)

Interactive 3D Structure

Interactive structure
rotate · zoom · variant + 5 Å neighbors
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AlphaFold wild-type wolframin · the variant site near residue 279 (N-terminal cytoplasmic (intrinsically disordered)) is highlighted.

Variant Assessment

Variant type
Synonymous
Schema
Silent
Silent — but near an exon boundary (splice effect possible)
Domain
N-terminal cytoplasmic (intrinsically disordered)
Status
—

Therapeutic Implication · Silent

No amino-acid change (P279 is unchanged), so there is no protein-level structural or stability effect. However, this codon sits within 3 residues of the exon junction near protein position 280 — close enough that the nucleotide change could perturb splicing. Worth a SpliceAI check (Wave 2); otherwise expected to be benign at the protein level.

Clinical Evidence

ClinVar classificationUncertain significance
Review statuscriteria provided, single submitter
Associated conditionsAutosomal dominant nonsyndromic hearing loss 6; WFS1-Related Spectrum Disorders
Population frequency (gnomAD v4)Absent from gnomAD v4
cDNA changec.837T>C
Protein consequenceP279=
ClinVar variantNM_006005.3(WFS1):c.837T>C (p.Pro279=)
ClinVar accessionVCV000907360
Last evaluated2018/01/13 00:00

Not observed in ~730k individuals — consistent with a rare allele (ACMG PM2_supporting).

Therapeutic Strategy Handoff · prediction

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Full Variant Card

P279= — WFS1 Molecular Atlas Card

Variant type: Synonymous (silent) Codon: position 279 (Proline, P) — amino acid unchanged Domain context: N-terminal cytoplasmic (intrinsically disordered)

Schema category: Silent — Silent — but near an exon boundary (splice effect possible)

No amino-acid change (P279 is unchanged), so there is no protein-level structural or stability effect. However, this codon sits within 3 residues of the exon junction near protein position 280 — close enough that the nucleotide change could perturb splicing. Worth a SpliceAI check (Wave 2); otherwise expected to be benign at the protein level.

Clinical evidence

  • Classification: Uncertain significance
  • Review status: criteria provided, single submitter
  • Associated conditions: Autosomal dominant nonsyndromic hearing loss 6; WFS1-Related Spectrum Disorders
  • cDNA change: c.837T>C
  • ClinVar accession: VCV000907360
  • Last evaluated: 2018/01/13 00:00
  • Submissions: 1

Card generated by wolfram-atlas-batch (synonymous pipeline) on 2026-06-08T02:51:57.834212Z. WFS1: UniProt O76024, AlphaFold v6. Synonymous variants carry no protein-structural effect.