The Target of EGR1 (TOE1) gene encodes the TOE1 deadenylase, which is essential for the maturation of Pol-II transcribed snRNAs in humans. Over a dozen missense mutations in the TOE1 gene have been linked to Pontocerebellar Hypoplasia Type 7 (PCH7), a rare but serious neurodevelopmental and neurodegenerative disease that leads to early mortality. The biochemical mechanisms for why these PCH7-linked mutations alter TOE1's biochemical characteristics remains vague. Here, we utilized AlphaFold predicted structures of TOE1 and biochemical characterizations to investigate the impact of TOE1 variants on TOE1's biochemical properties. We performed characterization of the thermal stability and activity of eleven PCH-linked TOE1 variants and found that eight variants have significant reduced protein thermal stability and only two variants impair TOE1's ribonuclease activity, particularly its exonuclease activity. Additionally, we found that the F148Y mutation impacts TOE1's oligomeric state in vitro and in vivo. Together, these results demonstrated that PCH-linked mutations of TOE1 impact many different aspects of TOE1 biochemistry, providing novel insights which may provide potential therapeutic strategies to treat PCH7 patients. In addition, these mutations provide a library of TOE1 variants that will be useful for future studies of TOE1 function and regulation.