BRAF mutations clustering in the CRD, particularly the Q257R variant, were predominantly associated with lymphopenia—especially T-cell lymphopenia—whereas MAP2K1 mutations, particularly Y130C variant, were frequently linked to monocytosis, reduced naïve and switched-memory B cells, and hypogammaglobulinemia, suggesting differential effects on lymphocyte development and immune cell homeostasis driven by dysregulated MAPK signaling. This evidence concerns the gene MAP2K1 and lymphopenia.