PseudoRA: A Novel Pseudogene ReAligner for Detecting SBDS Variants in Shwachman–Diamond Syndrome

variants in six patients (0.7%), whereas PseudoRA detected variants in 10 patients (1.2%), representing a 1.7-fold increase in diagnostic yield. PseudoRA identified seven additional cases, including low-VAF c.183_184delinsCT variants that had been missed or misclassified when assessed using conventional analysis. All variants detected via PseudoRA showed 100% concordance with Sanger sequencing. PseudoRA demonstrated comparable sensitivity to HapICE but enabled broader detection across multiple exons. PseudoRA improves the molecular diagnosis of SDS by recovering mismapped low-VAF variants and offers a scalable solution that can be integrated into conventional clinical pipelines.