The NM_000018.4 c.833_835del (p.Lys278del) variant in ACADVL is an in-frame deletion (removes amino acids Lys278) in exon 9/20 that is not predicted to impact splicing (SpliceAI: 0.01). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001 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). The c.833_835del variant is predicted to cause a change in the length of the protein (p.Lys278del) due to an in-frame deletion of an amino acid in a non-repeat region (PM4). This variant is reported in the literature in multiple individuals affected with very long-chain acyl-CoA dehydrogenase deficiency in both compound heterozygous and homozygous fashion, with at least one of whom displayed elevated C14:1 carnitine level (1.3 µmol/L) and reduced VLCAD enzyme levels (17% WT control), which is highly specific for VLCAD deficiency (PP4_Moderate, PMID: 19327992). This patient also carried a pathogenic variant c.1376G>A in trans (PM3 score = 1.0, PM3, PMID: 19327992). In summary, this variant meets the criteria to be classified as likely pathogenic 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: PM2_Supporting, PM4, PP4_Moderate, PM3 (ACADVL VCEP specifications version 1; approved November 9, 2021).