pathogenic variant
Genetic change that causes or predisposes to disease. Highest level of clinical significance in variant classification systems.
Full Definition
A genetic alteration that has been definitively demonstrated to cause a mendelian disorder or significantly predispose to disease through well-established biological mechanisms. Pathogenic variants represent the highest level of clinical significance in the five-tier ACMG classification system and are supported by multiple lines of robust evidence including functional studies, segregation analysis, population data, and peer-reviewed literature. Unlike variants of uncertain significance, pathogenic variants can be used confidently for clinical diagnosis, risk assessment, family screening, and medical management decisions. The identification of a pathogenic variant typically triggers specific clinical actions including genetic counseling, cascade testing of family members, and implementation of surveillance or treatment protocols.
Usage
Usage note: Reserve this term for variants with definitive evidence of pathogenicity; use 'likely pathogenic' for variants with strong but not conclusive evidence.
In Context
- "The laboratory identified a pathogenic variant in the BRCA1 gene associated with hereditary breast and ovarian cancer syndrome." — Genetic testing report
- "Clinical management protocols were initiated following confirmation of the pathogenic variant in the patient's genetic testing results." — Clinical genetics consultation