The 625G>A variant of the short-chain acyl-CoA dehydrogenase (SCAD) gene is considered to confer susceptibility for developing 'clinical SCAD deficiency' and appears to be common in the general population. To determine the frequency of the 625G>A variant in The Netherlands, we analysed 1036 screening cards of 5- to 8-day-old newborns and found 5.5% homozygous and 31.3% heterozygous for the 625G>A variant. An increased blood/plasma C4-carnitine concentration is considered to be one of the biochemical characteristics of SCAD deficiency. To explore the correlation of C4-carnitine levels with the 625G>A variant, we determined the C4-carnitine concentration, as well as the ratio of C4- to free carnitine, in blood spots from newborns, who were detected as homozygous, heterozygous or noncarriers for the gene variant. No significant differences were found between these groups. Our study demonstrates a high frequency of the 625G>A SCAD gene variant in the Dutch population, but no correlation to significantly increased C4-carnitine levels in blood spots taken between the 5th and 8th days of life. This latter observation might be the result of the relatively late timing of neonatal screening in our country, implying that fatty acid oxidation disorders may be missed at that stage. If the 625G>A variant is associated with clinical SCAD deficiency, the high frequency of the variant suggests a possible involvement of SCAD deficiency in the pathogenesis of common disorders, probably in relation to other genetic and/or environmental factors. However, homozygosity for the 625G>A variant might be only a biochemical phenomenon, representing a 'nondisease'.