Several studies from our and other groups have shown that for the NF1 gene, which is mutated in individuals with neurofibromatosis type 1 (NF1), the proportion of pathogenic variants that alter splicing, for simplicity named splice mutations throughout the paper, is among the highest found in human disease genes (Ars et al., 2000; Messiaen et al., 2000; Wimmer et al., 2007). The gene discussed is NF1; the disease is neurofibromatosis type 1.