In this study, we first performed a combination of exome sequencing and Sanger sequencing, and the results revealed a novel frameshift variant c.541dupC (NM_001042492.3, p.(Gln181Profs∗20)) in the NF1 gene in a Han Chinese family with NF1. Then, molecular analyses demonstrated the cells expressed the NF1 variant partially enhanced Ras activity and elevated cell proliferation and tumor formation. The gene discussed is NF1; the disease is neoplasm.