pathogenic variant
A genetic alteration that causes or predisposes to disease based on established clinical and functional evidence.
Full Definition
A DNA sequence variation that has been determined to cause disease or significantly increase disease risk through rigorous clinical and laboratory evidence. Pathogenic variants are classified using standardized guidelines that consider population frequency, functional studies, computational predictions, and clinical observations. In cancer genomics, pathogenic variants may be germline (inherited) or somatic (acquired) and directly contribute to cancer development or progression through disruption of normal cellular functions.
Usage
Usage note: Distinguished from 'likely pathogenic' in clinical variant classification; use precise ACMG terminology.
In Context
- "The BRCA1 c.5266dupC variant was classified as pathogenic based on functional and clinical evidence." — Genetic counseling report
- "Pathogenic variants in DNA repair genes increase hereditary cancer risk substantially." — Clinical genetics summary