The c.553G>A variant in ACADVL is a missense variant predicted to cause substitution of glycine by serine at amino acid 185 (p.Gly185Ser). This variant has been detected in at least 4 individuals with very long chain acyl CoA dehydrogenase (VLCAD) deficiency. Of those individuals, two were compound heterozygous for the variant and distinct pathogenic variants (PM3, PMIDs: 31620161, 17999356). Two patients with this variant displayed beta Oxidation Flux <20% of normal and at least one individual showed increased acylcarnitines, which is highly specific for very long chain acyl CoA dehydrogenase (VLCAD) deficiency (PP4_moderate, PMIDs: 17999356, 31620161, 22841441). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00005 in East Asian population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.971, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PM3, PP4_moderate, PM2_Supporting, PP3 (ACADVL VCEP specifications version 1; approved November 8, 2021).