The c.1349G>A (p.Arg450His) variant in ACADVL is a missense variant predicted to cause substitution of arginine by histidine at amino acid 450. At least one individual with this variant displayed reduced VLCAD activity, which is specific for very long chain acyl CoA dehydrogenase (VLCAD) deficiency (PP4, PMID: 11158518). This variant has been confirmed in trans to at least one likely pathogenic variant, not confirmed in trans to distinct likely pathogenic variants, and has been identified in the homozygous state in 2 individuals (PM3_Strong, PMID: 29519241, 15210884, 11158518, 9546340). The highest population minor allele frequency in gnomAD v2.0 is 0.00025 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 0.92, 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: PP4, PM3_Strong, PM2_Supporting, PP3 (ACADVL specifications version 1; approved November 8, 2021)