penetrance

Penetrance refers to the proportion of individuals who carry a particular genetic variant and express the associated phenotype. It is usually expressed as a percentage. If every carrier develops the trait or disease, penetrance is complete; if some carriers never manifest it, penetrance is incomplete or reduced. Penetrance is not the same as expressivity, which describes the severity or range of manifestations among those who express the trait.

Penetrance can vary with age, sex, and environmental factors, and may differ across populations. Some alleles show age-dependent penetrance, in which the likelihood of manifestation increases with age. Other modifiers, including other genes, lifestyle, or exposures, can increase or decrease penetrance. Conversely, some carriers never develop the condition despite harboring the variant, illustrating incomplete penetrance.

Examples are often cited in counseling; Huntington disease shows high penetrance with onset usually in adulthood and demonstrable age effect; BRCA1/BRCA2 pathogenic variants confer substantial but incomplete penetrance for breast and ovarian cancer; many dominant conditions thought to be fully penetrant in the pedigree may show reduced penetrance in the broader population.

Penetrance is estimated from observational data and is a key concept in genetic counseling, risk assessment, and interpretation of predictive genetic tests. Limitations include ascertainment bias, population stratification, and changing definitions of disease, so penetrance estimates are often context-specific and time-dependent.