When applied to cystic fibrosis, GENDULF successfully identifies multiple, previously established disease modifiers, including EHF, SLC6A14, and CLCA1. It is then utilized in spinal muscular atrophy (SMA) and predicts U2AF1 as a modifier whose low expression correlates with higher SMN2 pre‐mRNA exon 7 retention. Here, U2AF1 is linked to spinal muscular atrophy.