The NM_000018.4(ACADVL): c.1076C>T (p.Ala359Val) variant in ACADVL is a missense variant predicted to cause substitution of alanine by valine at amino acid 359 (p.Ala359Val). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00008 in African/African American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). This variant is reported in the literature in an individual apparently affected with very long-chain acyl-CoA dehydrogenase deficiency, displaying elevated C14:1 carnitine level (1.65 µmol/L) during newborn screening, which is highly specific for VLCAD deficiency (PP4_Supporting, PMID: 27209629). This patient also carried a pathogenic variant c.848T>C (p.V283A) in compound heterozygous fashion (in trans, PM3 score = 1.0, PM3, PMID: 27209629). In addition, this variant has been reported in the literature in 6 patients with an abnormal newborn screen who are apparently heterozygous carriers for the variant (PMIDs: 26385305, 29111448), but this information is insufficient to use toward classification. The computational predictor REVEL gives a score of 0.76, which is above the threshold of 0.75, evidence that correlates with impact to ACADVL function (PP3). Due to limited evidence, this variant is classified as a variant of uncertain significance for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PP3, PM3, PM2_Supporting, PP4_Supporting (ACADVL VCEP specifications version 1; approved November 9, 2021).