Illumina has unveiled PromoterAI, a groundbreaking AI algorithm designed to accurately identify pathogenic regulatory genetic variants in the noncoding regions of the human genome, specifically within promoter segments. A recent study published in Science demonstrated that these previously overlooked promoter variants contribute up to 6% of the genetic causes of rare diseases. This deep learning technology aims to significantly improve the diagnostic rate for rare diseases, as current exome sequencing only provides an accurate diagnosis for about 30% of patients, with many answers hidden in the vast noncoding regions. PromoterAI interprets the genetic sequence of promoters to reveal how mutations can disrupt gene expression, thereby offering precise diagnoses for more patients. When combined with other Illumina AI tools like SpliceAI and PrimateAI-3D, the diagnostic yield for rare diseases can effectively double compared to relying solely on protein-truncating variants. PromoterAI is now accessible through Illumina Connected Software and as part of DRAGEN™ secondary analysis, with precomputed scores for all human promoter single-nucleotide variants freely available for academic and noncommercial research, empowering researchers and clinicians to accelerate breakthroughs in precision medicine.