Structural distance at the tRNA synthetase active site interface predicts pathogenicity but is captured by AlphaMissense and EVE except among score-ambiguous va... (opens in new tab)

Variants of uncertain significance have accumulated as genomic sequencing has become more widespread, which complicates rare disease diagnosis and requires substantial resources for re-evaluation. Aminoacyl-tRNA synthetases (ARSs) are a protein family with extensive variant data and well-characterized disease associations, making them an ideal system for investigating the relationship between variant location and pathogenicity. Using structural distance measurements to the ARS-tRNA binding in...