STAT1 variants demonstrate 2 distinct mechanistic consequences: AR loss-of-function mutations abolish STAT1 phosphorylation or DNA binding in response to IFN-γ, causing MSMD, while AD gain-of-function variants sustain STAT1 phosphorylation, impair Th17 differentiation, and result in chronic mucocutaneous candidiasis. This evidence concerns the gene IFNG and Mendelian susceptibility to mycobacterial diseases.