ClinVar is the primary reference database for variant classification in clinical practice. But for many rare disease genes, it captures only a fraction of what the published literature actually
contains. In Fabry disease, most clinically actionable GLA variants, those classified as pathogenic or likely pathogenic, were absent from ClinVar before systematic literature curation.
When the evidence base is incomplete, every variant classification decision carries more uncertainty. Patients wait longer. Labs sign out reports with less confidence.
This poster, presented at the European Human Genetics Conference (ESHG 2026), documents the impact of submitting 1,342 curated GLA variants from Mastermind to ClinVar. Using AI- powered full-text search and expert curation following ACMG/AMP guidelines, the Genomenon team identified 753 variants from published literature not previously in ClinVar, of which 613 (81.4%) were pathogenic or likely pathogenic. Submission produced a 129% increase in P/LP variants in ClinVar (from 481 to 1,103). An additional 37 previously submitted VUS were reclassified to P/LP status by expert curators, demonstrating the clinical enrichment that literature-derived evidence delivers.
The result: a more complete ClinVar reference for GLA variants, supporting more confident
diagnoses and more consistent variant interpretation across diagnostic labs globally.
