PEAK: a phenotype-based classification of genetic variants.

PEAK variants are associated with more severe clinical phenotypes than heterozygous null alleles in the same gene.

• Why it matters: Current variant classifications lack the ability to distinguish variants based on clinical severity within the same gene, limiting precise genotype-phenotype interpretation and therapeutic targeting.
• What they did: The authors introduce PEAK as a new term for variants linked to more severe phenotypes than heterozygous null alleles, aiming to improve classification and identify candidates for allele-selective therapies.
• The result: This phenotype-exceeding-(mono)allelic-knockout designation may enhance understanding of genotype-phenotype relationships and support the development of targeted treatments.