The c.1138G>T variant in MYOC is a missense variant predicted to cause substitution of Aspartic Acid by Tyrosine at amino acid 380 (p.Asp380Tyr). This variant was not found in any genetic ancestry group of gnomAD (v4.1.0), meeting the ≤ 0.0001 threshold set for PM2_Supporting in a genetic ancestry group of at least 10,000 alleles. The REVEL score = 0.964, which met the ≥ 0.932 threshold for PP3_Strong, predicting a damaging effect on MYOC function. The Asp380Tyr protein had increased insolubility and reduced secretion levels compared to wild type myocilin protein in this study (J Hulleman pers. comm.). The assays met the OddsPath threshold for PS3_Moderate (> 4.3) (when combined with PMID: 35196929), indicating that this variant did impact protein function. Only 1 proband with primary open angle glaucoma had been reported (PMID: 31302906), not meeting the ≥ 2 probands threshold required to meet PS4_Supporting. Another missense variant (c.1139A>C, p.Asp380Ala, Grantham score (GS) = 126) in the same codon has been classified as pathogenic for juvenile open angle glaucoma (JOAG) by the ClinGen Glaucoma VCEP. Additionally, 2 other missense variants (c.1138G>C, p.Asp380His, GS = 81) and (c.1139A>G, p.Asp380Gly, GS = 94) have been classified as likely pathogenic for JOAG by the VCEP. The c.1138G>T, p.Asp380Tyr variant has a higher Grantham score (= 160) than the previously classified amino acid changes, was not predicted to affect splicing as assessed with SpliceAI (≤ 0.2), and met PP3, meeting the conditions for PM5_Strong to apply. In summary, this variant met the criteria to receive a score of 8 and to be classified as likely pathogenic (likely pathogenic classification range 6 to 9, adapted from PMID: 32720330) for primary open angle glaucoma based on the ACMG/AMP criteria met, as specified by the ClinGen Glaucoma VCEP (v2.1.0, 2 October 2025): PM5_Strong, PP3_Strong, PS3_Moderate, PM2_Supporting (PP3 and PM5 capped at 5 points).