Although this NF1 variant exhibits a high CADD score (24.6), has been reported in one case of lung cancer (Redig et al. 2016), and is located within the cysteine-serine–rich domain, a region where several missense mutations associated with breast cancer and neurofibromatosis have been identified (Koczkowska et al. 2018), its pathogenic status—and potential for positive selection—remains uncertain. This evidence concerns the gene NF1 and neurofibromatosis.