Variant reclassification is a critical process in clinical genetics that involves reassessing the pathogenicity of genetic variants over time. This review explores the medical and scientific literature on variant reclassification, focusing on its clinical implications. Variant reclassification is driven by accumulating evidence from diverse sources, leading to reclassification rates ranging from 3.6% to 58.8%. Recent studies show that significant changes can occur within one year of initial classification, highlighting the importance of early and accurate variant assignment for clinical care. Variants of uncertain significance (VUS) are particularly problematic, as they lack clear categorization but have influenced patient treatment despite recommendations against it. Addressing VUS reclassification is essential to enhance the credibility of genetic testing and its clinical impact. Factors affecting reclassification include standardized guidelines, clinical phenotype-genotype correlations through deep phenotyping and ancestry studies, large-scale databases, and bioinformatics tools. As genomic databases grow and knowledge advances, reclassification rates are expected to change, reducing discordance in future classifications. Variant reclassification affects patient diagnosis, precision therapy, and family screening. Understanding influencing factors and adopting standardized guidelines are vital for precise molecular genetic diagnoses, ensuring optimal patient care and minimizing clinical risk. The 2015 ACMG/AMP guidelines are the most widely used for variant classification, but they are not enforced. Variant reclassification is documented to be reduced for variants classified after 2016 compared with those classified before 2016, possibly due to the release of the 2015 guidelines. Older classifications often show discordance between laboratories, while recent classifications are more consistent. Variants reclassified between laboratories may predict future reclassification. Standardized guidelines, segregation analysis, clinical presentation, ancestry, databases, and bioinformatics tools all play roles in variant reclassification. Genome reanalysis using improved techniques and updated guidelines can lead to reclassification of previously identified variants. Variant reclassification can significantly impact clinical outcomes, including medical management, surveillance recommendations, and treatment decisions. Ethical considerations regarding recontacting patients after variant reclassification remain unclear. The responsibility for recontacting patients and informing them of updated classifications is not well-defined. Clinical genetics services are evolving to address ongoing variant reanalysis and patient follow-up, emphasizing the need for continued genetic counseling to stay updated with variant reclassification and ensure optimal patient care. In conclusion, variant reclassification is an evolving field with significant clinical implications. It can affect lifelong medical surveillance, prompt prophylactic treatment, and improve precision medicine. As genomic technologies advance, more accurate variant classification is expected, enhancing molecular diagnoses. Until then, variant reclassification may represent a shift in how clinical genetics services are provided, emphasizing long-term patient follow-up rather than point-of-service appointments.Variant reclassification is a critical process in clinical genetics that involves reassessing the pathogenicity of genetic variants over time. This review explores the medical and scientific literature on variant reclassification, focusing on its clinical implications. Variant reclassification is driven by accumulating evidence from diverse sources, leading to reclassification rates ranging from 3.6% to 58.8%. Recent studies show that significant changes can occur within one year of initial classification, highlighting the importance of early and accurate variant assignment for clinical care. Variants of uncertain significance (VUS) are particularly problematic, as they lack clear categorization but have influenced patient treatment despite recommendations against it. Addressing VUS reclassification is essential to enhance the credibility of genetic testing and its clinical impact. Factors affecting reclassification include standardized guidelines, clinical phenotype-genotype correlations through deep phenotyping and ancestry studies, large-scale databases, and bioinformatics tools. As genomic databases grow and knowledge advances, reclassification rates are expected to change, reducing discordance in future classifications. Variant reclassification affects patient diagnosis, precision therapy, and family screening. Understanding influencing factors and adopting standardized guidelines are vital for precise molecular genetic diagnoses, ensuring optimal patient care and minimizing clinical risk. The 2015 ACMG/AMP guidelines are the most widely used for variant classification, but they are not enforced. Variant reclassification is documented to be reduced for variants classified after 2016 compared with those classified before 2016, possibly due to the release of the 2015 guidelines. Older classifications often show discordance between laboratories, while recent classifications are more consistent. Variants reclassified between laboratories may predict future reclassification. Standardized guidelines, segregation analysis, clinical presentation, ancestry, databases, and bioinformatics tools all play roles in variant reclassification. Genome reanalysis using improved techniques and updated guidelines can lead to reclassification of previously identified variants. Variant reclassification can significantly impact clinical outcomes, including medical management, surveillance recommendations, and treatment decisions. Ethical considerations regarding recontacting patients after variant reclassification remain unclear. The responsibility for recontacting patients and informing them of updated classifications is not well-defined. Clinical genetics services are evolving to address ongoing variant reanalysis and patient follow-up, emphasizing the need for continued genetic counseling to stay updated with variant reclassification and ensure optimal patient care. In conclusion, variant reclassification is an evolving field with significant clinical implications. It can affect lifelong medical surveillance, prompt prophylactic treatment, and improve precision medicine. As genomic technologies advance, more accurate variant classification is expected, enhancing molecular diagnoses. Until then, variant reclassification may represent a shift in how clinical genetics services are provided, emphasizing long-term patient follow-up rather than point-of-service appointments.