GNAS and McCune-Albright syndrome: FD/MAS is caused by activating mutations in the GNAS locus, encoding the Gsα protein.4 The most common variants, c.602G>A (p.R201H) and c.601C>T (p.R201C), cause constitutive activation of Gsα by inhibiting its GTP hydrolase activity, leading to persistently elevated intracellular cAMP and increased downstream cAMP pathway activity.