Background <p>Primary carnitine deficiency (PCD) is an autosomal recessive rare disorder of carnitine cycle and carnitine transport caused by pathogenic variants in the <i>SLC22A5</i> gene. The prevalence of PCD is unclear. This study aimed to estimate the carrier frequency and genetic prevalence of PCD using Genome Aggregation Database (gnomAD) data.</p> Methods <p>The pathogenicity of <i>SLC22A5</i> variants was interpreted according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. The minor allele frequency (MAF) of the variants of the <i>SLC22A5</i> gene in 807,162 individuals was examined to estimate the global prevalence of PCD in nine ethnicities: African/African American (afr), Admixed American (amr), East Asian (eas), Non-Finnish European (nfe), South Asian (sas), Ashkenazi Jewish (asj), Middle Eastern (mid), Finnish (fin) and Remaining individuals (rmi). The global and population-specific carrier frequency and genetic prevalence of PCD were calculated using the Hardy–Weinberg equation.</p> Results <p>Total of 213 pathogenic/likely pathogenic variants (PV/LPV) of the <i>SLC22A5</i> gene were identified according to the ACMG standards and guidelines. The global carrier frequency and genetic prevalence of PCD were 10.6 per thousand (1/95) and 28.2 per million (1/35427), respectively.</p> Conclusions <p>The prevalence of PCD is estimated to be 1/35,000 globally, with a range of between 1/450,000 and 1/20,000 depending on ethnicity.</p>