A variant of uncertain significance (VOUS, VUS) is an alteration in a gene (distinct from the reference sequence) that may or may not be disease-causing or associated with increased risk of an abnormal phenotype; the identification of a variant of uncertain significance neither confirms nor rules out a diagnosis. A variant of uncertain significance does not meet criteria to be classified as pathogenic or benign according to the five-tier system for describing the clinical significance of genetic variants (see Related terms). Sequence analysis may identify multiple variants of uncertain significance in a given gene or hundreds to thousands in the human exome.

Related terms: benign variant; likely benign; likely pathogenic; pathogenic variant