The c.644_647del (p.Phe214_Cys215insTer) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 8/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). The highest population minor allele frequency in gnomAD v3.1.2 is 0.00006549 in Latino/Admixed American population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). At least one patient with this variant displayed enzyme levels which is highly specific for VLCAD (PP4, PMID: 15210884). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive very long chain acyl-CoA dehydrogenase (VLCAD) deficiency based on the ACMG/AMP criteria applied, as specified by the PVS1, PM2, PP4. (ACADVL VCEP specifications version 1; approved November 8, 2021).