The c.1321A>G variant in the hepatocyte nuclear factor 4-alpha gene, HNF4A, causes an amino acid change of isoleucine to valine at codon 441 (p.(Ile441Val)) of NM_175914.4. This variant has a Grpmax Filtering allele frequency in gnomAD 2.1.1 of 0.0005025, which is greater than the MDEP threshold for BA1 (BA1). This variant was identified in an individual with a clinical history highly specific for HNF4A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF1A, and GAD negative) (PP4_Moderate, internal contributors). There is evidence in vitro that this variant has identical transactivation activity to wildtype, indicating that this variant does not impact protein function (BS3_Supporting, PMID: 30191603). This variant does not segregate with diabetes in three families (BS4; internal lab contributors, PMIDs: 25905084, 10227563, 33324081). This variant was identified in a patient with an alternate molecular basis for disease (BP5; internal lab contributors). This variant has a REVEL score of 0.354, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF1A function. In summary, c.1321A>G p.(Ile441Val) meets the criteria to be classified as benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 2.0.0, approved 10/11/2023): BA1, PP4_Moderate, BS3_Supporting, BS4, BP5.