The c.642_643del (p.Phe214LeufsTer38) variant in ACADVL is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 9/20 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMIDs 9973285, 11590124). At least one patient with this variant displayed increased acylcarnitine levels, which is highly specific for very long chain acyl CoA dehydrogenase (VLCAD) deficiency (PP4, PMID: 31620161). Additionally, two individuals carried a distinct likely pathogenic variant not confirmed to be in trans, but one of these individuals was not confirmed by biochemical testing to be affected with VLCAD deficiency (PMID: 35400565). The highest population minor allele frequency in gnomAD v3.1.2 is 0.00001470 in European (non-Finnish) population, which is lower than the ClinGen ACADVL Variant Curation Expert Panel threshold (<0.001) for PM2_Supporting, meeting this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive VLCAD deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen ACADVL Variant Curation Expert Panel: PVS1, PM2_Moderate, PP4 (ACADVL VCEP specifications version 1; approved November 8, 2021).