Interleukin 7 (IL-7) is a critical cytokine that plays a fundamental role in B- and T-cell development and in acute lymphoblastic leukemia (ALL). Its receptor (IL7R) is a transmembrane heterodimer formed by the IL7Rα and the IL2Rγ chain (γc). The IL7R signals through the JAK/STAT pathway. Loss-of-function mutations and some polymorphisms of the IL7Rα were associated to immunodeficiency and inflammatory diseases, respectively. Gain-of-function mutations were described in T-cell ALL and in high risk precursor B-cell ALL. Most confirmed loss-of-function mutations occur in the extracellular part of the IL7Rα while oncogenic mutations are exclusively found in the extracellular juxtamembrane (EJM) or transmembrane regions. Oncogenic mutations promote either IL7Rα/IL7Rα homodimerization and constitutive signaling, or increased affinity to γc or IL-7. This work presents a review on IL7Rα polymorphisms/mutations and attempts to present a classification based on their structural consequences and resulting biological activity.