Our cohort’s patients with novel STAT3 variants presented with c.1295 T > C (p.Val432Ala)-related hypereosinophilia, c.31G > A (p.Asp11Asn)- and c.1324G > C (p.Glu442Gln)-associated ALPS, and hepatosplenomegaly. Here, STAT3 is linked to Hepatosplenomegaly.