Expanded carrier screening in a Southwestern Chinese population indicates East Asian specific low-frequency pathogenic variants account for nearly half of the at-risk couple rate

BACKGROUND: The optimal disease spectrum for carrier screening (CS) remains debated. We aimed to characterise the carrier landscape and quantify the at-risk couple rate (ACR) components in a Chinese population to guide panel design. METHODS: Using a 334-gene expanded CS panel, we screened 3748 individuals from Sichuan, China. Pathogenic/likely pathogenic (P/LP) variants were classified by allele frequency and geographic specificity. RESULTS: alone contributed 20% to the AR ACR. CONCLUSION: East Asian-specific low-frequency variants significantly contribute to the carrier burden in this population, accounting for nearly half of the AR risk. These findings provide empirical evidence that CS panels should prioritise population-specific carrier frequencies over global data to maximise clinical utility in regions with specific ethnic compositions.