In-frame BRAF exon 12 deletions are increasingly identified in various tumor types. The resultant BRAF^(Δβ3-αC) oncoproteins usually lack five amino acids in the β3-αC helix linker and sometimes contain de novo insertions. The dimerization status of BRAF^(Δβ3-αC) oncoproteins, their precise pathomechanism, and their direct druggability by RAF inhibitors (RAFi) has been under debate. Here, we functionally characterize BRAF^(ΔLNVTAP>F) and two novel mutants, BRAF^(delinsFS) and BRAF^(ΔLNVT>F), …