In this study, we analyzed phenotypic manifestations and clinical course of cystic fibrosis (CF) in patients with the pathogenic variant L138ins of the CFTR gene. The L138ins variant is rarely detected in CF patients worldwide, but is quite common in different regions of the Russian Federation, particularly in the Middle Urals. Before the neonatal screening implementation, the majority of CF patients with the L138ins variant were diagnosed late because of the mild disease course and dubious results of sweat tests. Such patients usually have elevated levels of immunoreactive trypsinogen (IRT) in the neonatal period, which enables early diagnosis; however, false-negative results in CF patients have also been reported. There were cases of male infertility among CF patients with the L138ins variant, while women had their reproductive function preserved. There were also cases of asymptomatic pancreatic hyperenzymemia in children. Respiratory infections caused by Pseudomonas aeruginosa are not very common in this group of patients. However, adult patients have more severe respiratory manifestations (even with a fatal outcome) than children. Thus, despite the mild disease phenotype in patients with the L138ins variant, the residual function of the protein is not sufficient to ensure normal functioning of lungs. Key words: cystic fibrosis, pathogenic CFTR variants, L138ins