The m.13042G>A (p.A236T) variant in MT-ND5 has been reported in six unrelated individuals with primary mitochondrial disease with onset ranging from the first year of life to adulthood; and features variably consistent CPEO, LHON, MERRF/MELAS, Leigh-like syndrome (PS4_moderate; PMIDs: 15767514; 17400793; 31996177; 16816025). This variant segregated with disease in a family with LHON as the proband's heteroplasmy was 41% in urine and his affected sister had the variant present at 39% in urine and 91% in muscle. There were unaffected sisters (heteroplasmy levels of 4% and 20% in urine) as well as an unaffected brother with the variant present at 43% urine. In another family, this variant segregated with Leigh syndrome in the proband (heteroplasmy level in in blood was 77%, in muscle was 84%, in fibroblasts was 86%); the healthy mother harbored the variant in hair (25%) and blood (11%); and the proband’s maternal grandmother was found to have the variant at < 2% in blood and between 4-6% in muscle (PP1_moderate, PMIDs: 16816025 17400793). There are no reports of confirmed de novo occurrences to our knowledge. This variant is absent in the Helix dataset and gnomAD v3.1.2, and there is only one occurrence in the GenBank dataset (PM2_supporting). The computational predictor APOGEE gives a consensus rating of pathogenic with a score of 0.85 (Min=0, Max=1), which predicts a damaging effect on gene function (PP3). There are no cybrids, single fiber studies, or other functional assays reported on this variant. In summary, this variant meets criteria to be classified as likely pathogenic for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 Mitochondrial Disease Variant Curation Expert Panel on June 13, 2022. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): PS4_moderate, PP1_moderate, PP3, PM2_supporting.