We identified two heterozygous nonsense variants in COL5A1 in two patients presenting with classical EDS: one of them (c.1884_1891del; p.(Asp629Phefs16Ter) is described in this report for the first time, in patient P9, while the other (c.2374C > T; p.(Arg792Ter) [46]) was observed in a compound heterozygous state with a novel missense VUS in the same gene: (c.4030C > T; p.(Pro1344Ser)) in patient P14 (Table 1). The gene discussed is COL5A1; the disease is Ehlers-Danlos syndrome.