This study investigates the impact of rare coding variants on depression using whole-exome sequencing data from 320,356 UK Biobank participants. The analysis is based on seven different definitions of depression, including survey, questionnaire, and electronic health records. The results show that the burden of rare damaging coding variants in loss-of-function intolerant genes is significantly associated with depression risk across various definitions. Genetic correlations between depression definitions based on rare and common variants are different, indicating varying genetic relationships. The effects of rare coding variant burden and polygenic risk score (PRS) on depression risk are additive. Gene set burden analyses reveal overlapping rare genetic components with developmental disorders, autism, and schizophrenia. The study provides insights into the contribution of rare coding variants to depression and their relationships with neurodevelopmental disorders.This study investigates the impact of rare coding variants on depression using whole-exome sequencing data from 320,356 UK Biobank participants. The analysis is based on seven different definitions of depression, including survey, questionnaire, and electronic health records. The results show that the burden of rare damaging coding variants in loss-of-function intolerant genes is significantly associated with depression risk across various definitions. Genetic correlations between depression definitions based on rare and common variants are different, indicating varying genetic relationships. The effects of rare coding variant burden and polygenic risk score (PRS) on depression risk are additive. Gene set burden analyses reveal overlapping rare genetic components with developmental disorders, autism, and schizophrenia. The study provides insights into the contribution of rare coding variants to depression and their relationships with neurodevelopmental disorders.