The c.871C>A variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of proline to threonine at codon 291 (p.(Pro291Thr)) of NM_000545.8. The Grpmax filtering allele frequency of this variant in gnomAD v4.1.0 is 0.000017, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting and BS1; thus, neither criterion will be applied. This variant was identified in three unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4 cannot be applied because this number is below the ClinGen MDEP threshold and the variant has a MAF in gnomAD that is above the PM2_Supporting cutoff (PMIDs: 18003757, 30455330; internal lab contributors). This variant was identified in an individual with a clinical history highly specific for HNF1A-monogenic diabetes (>50% MODY probability calculator result and negative HNF4A testing; negative diabetes autoantibodies) (PP4_Moderate; internal lab contributors). This variant segregated with diabetes with three informative meioses in two families (PP1_Moderate; PMID: 22432108; internal lab contributors). This variant has a REVEL score of 0.587, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on HNF1A function. Functional studies of this variant are also inconclusive, as the variant results in transactivation activity 59.2% of WT, which falls between the cutoffs for PS3 and BS3. However, DNA binding activity and protein expression are not significantly different from WT (PMID: 18003757, Gloyn group)​. In summary, c.871C>A meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 3.0.0, approved 6/30/2025): PP1_moderate, PP4_moderate.