Schematic representation of WAS disease risk prior to vs after Vallée et al. (Left) Depiction of what was known about WAS disease risk prior to the current publication. WAS comprised a broad spectrum of disease states, and disease severity was estimated using the WAS score. There were no biomarkers to predict disease severity or outcome. (Middle) In this publication, the authors used WAS variants themselves as disease biomarkers, defining class I vs class II variants based on a large cohort of 577 patients with WAS-consistent phenotypes from 63 centers in 26 countries. (Right) Class I variants (green) were comprised of missense variants in exons 1 or 2, or the hot spot intronic variant c.559+5G>A. Individuals with these variants had a less severe phenotype, characterized by later age of diagnosis, lower WAS score, older age of first procedure, later onset of disease complications, and better overall survival compared with all other variants, which were grouped as class II. Created with BioRender.com.