HNF1B (Hepatocyte nuclear factor 1-beta) variants and mutations
HNF1B (also known as Hepatocyte nuclear factor 1-beta) is a human protein-coding gene encoding a hepatocyte nuclear factor 1-beta protein. It controls developmental and metabolic gene programs in kidney, pancreas, liver, and genital tract. Haploinsufficiency or intragenic pathogenic variants cause a multisystem disorder often featuring renal cysts or malformations, maturity-onset diabetes of the young, hypomagnesemia, and genital abnormalities. This analysis covers 996 HNF1B variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes renal cysts and diabetes syndrome, type 2 diabetes mellitus, and maturity-onset diabetes of the young. Example HNF1B variants include M1I, K4R, and K4T.
Variant analysis overview
- Gene: HNF1B
- Protein: Hepatocyte nuclear factor 1-beta
- UniProt accession: P35680
- Organism: Homo sapiens
- Variants analyzed: 996
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 734 unspecified-consequence records; 1 stop retained variant; 160 missense variants; 81 synonymous variants; 8 frameshift variants; 2 in-frame deletions; 2 splice-region variants; 7 stop-gained variants; 1 substitution
- Prediction scores: 746 variants have prediction scores (75% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: renal cysts and diabetes syndrome, type 2 diabetes mellitus, maturity-onset diabetes of the young, nonpapillary renal cell carcinoma, MODY, diabetes mellitus, prostate carcinoma, neurodegenerative disease, renal cell carcinoma, hereditary clear cell renal cell carcinoma, prostate cancer, transient neonatal diabetes mellitus.
Protein structure and variant hotspots
- Protein features: 2 domains; 4 post-translational modification sites.
- Structural context: 155 variants have structural context.
- PTM context: 7 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable HNF1B variants
Examples include M1I, K4R, K4T, L5P, S7L, Q9*, Q10K, E11G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs2511853757, ClinGen CA398755454, ClinVar RCV000787261, ClinGen CA398755458, Pathogenic, Renal cysts and diabetes syndrome
- K4R (p.Lys4Arg), rs768909646, ClinGen CA398755386, ClinVar RCV003228641, ExAC rs768909646, CADD 22.90, PolyPhen-2 0.37, Uncertain significance, Type 2 diabetes mellitus
- K4T (p.Lys4Thr), ExAC rs768909646, TOPMed rs768909646, gnomAD rs768909646, CADD 24.30, PolyPhen-2 0.54, Uncertain significance
- L5P (p.Leu5Pro), gnomAD rs1316368640
- S7L (p.Ser7Leu), Ensembl rs2034126576, CADD 22.50, PolyPhen-2 0.25
- Q9* (p.Gln9Ter), rs2511853625, ClinGen CA398755209, ClinVar RCV003073271, Pathogenic
- Q10K (p.Gln10Lys), Ensembl rs2147600595
- E11G (p.Glu11Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L12F (p.Leu12Phe), rs1285239018, TOPMed rs1285239018, gnomAD rs1285239018, ClinGen CA398755124, CADD 28.80, PolyPhen-2 1.00, Conflicting interpretations, Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal
- A15T (p.Ala15Thr), gnomAD rs1282378255, CADD 27.40, PolyPhen-2 1.00
- A15V (p.Ala15Val), rs2511853437, ClinGen CA398754997, ClinVar RCV003553299, ClinVar RCV005240798, Uncertain significance, not specified; not provided
- S18R (p.Ser18Arg), TOPMed rs2034125548, CADD 22.90, PolyPhen-2 0.17
- S19F (p.Ser19Phe), ExAC rs775848522, TOPMed rs775848522, gnomAD rs775848522, CADD 32.00, PolyPhen-2 1.00, Uncertain significance, not provided
- S19Y (p.Ser19Tyr), ExAC rs775848522, TOPMed rs775848522, gnomAD rs775848522, Uncertain significance
- G20R (p.Gly20Arg), rs1052557621, ClinGen CA290293293, ClinVar RCV002465370, TOPMed rs1052557621, CADD 28.70, PolyPhen-2 1.00, Likely risk allele, Maturity-onset diabetes of the young
- V21D (p.Val21Asp), TOPMed rs2034124849
- V21I (p.Val21Ile), rs1304695155, ClinGen CA398754820, ClinVar RCV000519912, ClinVar RCV002464245, CADD 21.20, PolyPhen-2 0.35, Uncertain significance/Uncertain risk allele, Maturity-onset diabetes of the young; not provided
- T22A (p.Thr22Ala), TOPMed rs1347700026
- K23R (p.Lys23Arg), rs2511853122, ClinGen CA398754786, ClinVar RCV003661649, ClinVar RCV005014821, Uncertain significance, not provided; Nonpapillary renal cell carcinoma; Renal cysts and diabetes syndro
- E24V (p.Glu24Val), Ensembl rs1023804221, CADD 26.20, PolyPhen-2 0.86
- V25L (p.Val25Leu), rs139107479, ClinGen CA214365, ClinVar RCV000030533, ClinVar RCV000345835, CADD 19.40, PolyPhen-2 0.22, Conflicting interpretations, not specified; Maturity-onset diabetes of the young; not provided
- V27F (p.Val27Phe), NCI-TCGA TCGA novel, CADD 20.00, PolyPhen-2 0.17, Variant assessed as somatic; moderate impact.
- V27L (p.Val27Leu), rs747555052, ExAC rs747555052, TOPMed rs747555052, gnomAD rs747555052, CADD 15.20, PolyPhen-2 0.00, Uncertain significance, not provided
- A29V (p.Ala29Val), TOPMed rs1200049050
- L30* (p.Leu30Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L30S (p.Leu30Ser), rs2511852918, ClinGen CA398754638, ClinVar RCV004555443, Uncertain significance, Renal cysts and diabetes syndrome
- E31K (p.Glu31Lys), gnomAD rs1480946255, CADD 23.20, PolyPhen-2 0.37
- E32K (p.Glu32Lys), rs2511852824, ClinGen CA398754586, ClinVar RCV003154697, CADD 25.00, PolyPhen-2 0.13, Benign, Ovarian cancer
- L33F (p.Leu33Phe), TOPMed rs2034122976, CADD 22.30, PolyPhen-2 0.57
- L33W (p.Leu33Trp), TOPMed rs1254680949
- P35S (p.Pro35Ser), Ensembl rs1263893732, CADD 24.60, PolyPhen-2 0.49
- S36F (p.Ser36Phe), rs544890850, ClinGen CA8519156, ClinVar RCV000787256, ClinVar RCV001248883, CADD 24.10, PolyPhen-2 0.45, Conflicting interpretations, Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal
- P37L (p.Pro37Leu), gnomAD rs1242776529, CADD 28.30, PolyPhen-2 0.59
- N38D (p.Asn38Asp), 1000Genomes rs550362662, ExAC rs550362662, gnomAD rs550362662, CADD 22.30, PolyPhen-2 0.01
- N38K (p.Asn38Lys), Ensembl rs2034122027
- F39L (p.Phe39Leu), gnomAD rs1262317733, CADD 19.00, PolyPhen-2 0.30
- F39Y (p.Phe39Tyr), ESP rs373847943, ExAC rs373847943, TOPMed rs373847943, gnomAD rs373847943, CADD 21.90, Uncertain significance, Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal
- G40E (p.Gly40Glu), rs2511852471, ClinGen CA398754435, ClinVar RCV003894414, Uncertain significance, HNF1B-related disorder
- G40R (p.Gly40Arg), rs753701914, ExAC rs753701914, gnomAD rs753701914, CADD 24.50, PolyPhen-2 1.00, Variant assessed as somatic; moderate impact.
- V41M (p.Val41Met), gnomAD rs1293365273, CADD 24.80, PolyPhen-2 0.91
- L43V (p.Leu43Val), rs533489657, 1000Genomes rs533489657, ExAC rs533489657, TOPMed rs533489657, CADD 22.30, PolyPhen-2 0.47, Uncertain significance, not provided
- E44K (p.Glu44Lys), rs1362125211, ClinGen CA398754352, ClinVar RCV000787253, TOPMed rs1362125211, AlphaMissense 0.57, MetaLR 0.92, Uncertain significance, Renal cysts and diabetes syndrome
- E44Q (p.Glu44Gln), rs1362125211, ClinGen CA398754349, ClinVar RCV002297895, NCI-TCGA TCGA novel, AlphaMissense 0.57, MetaLR 0.92, Uncertain significance, not provided
- T45M (p.Thr45Met), ExAC rs760528165, CADD 25.70, PolyPhen-2 0.56
- L46R (p.Leu46Arg), Ensembl rs1598854694
- P47L (p.Pro47Leu), rs193922483, ExAC rs193922483, TOPMed rs193922483, gnomAD rs193922483, CADD 25.00, PolyPhen-2 0.42, Uncertain significance, Type 2 diabetes mellitus; Nonpapillary renal cell carcinoma; Renal cysts and dia
- P47S (p.Pro47Ser), ExAC rs767558546, gnomAD rs767558546, CADD 23.00, PolyPhen-2 0.24
- P47T (p.Pro47Thr), ExAC rs767558546, gnomAD rs767558546, CADD 22.90, PolyPhen-2 0.38
- L48P (p.Leu48Pro), Ensembl rs894083743, CADD 25.50, PolyPhen-2 0.89
- S49A (p.Ser49Ala), ExAC rs775376615, TOPMed rs775376615, gnomAD rs775376615, CADD 22.70, PolyPhen-2 0.17
- S49C (p.Ser49Cys), rs770078634, ExAC rs770078634, gnomAD rs770078634, ClinGen CA8519147, CADD 27.60, PolyPhen-2 0.91, Uncertain significance/Uncertain risk allele, Maturity-onset diabetes of the young; not provided
- S49T (p.Ser49Thr), ExAC rs775376615, TOPMed rs775376615, gnomAD rs775376615
- P50A (p.Pro50Ala), ExAC rs746036863, TOPMed rs746036863, gnomAD rs746036863, CADD 23.90, PolyPhen-2 1.00
- P50S (p.Pro50Ser), ExAC rs746036863, TOPMed rs746036863, gnomAD rs746036863, CADD 26.60, PolyPhen-2 1.00
- S52N (p.Ser52Asn), gnomAD rs1379668860, CADD 19.20, PolyPhen-2 0.00
- S52R (p.Ser52Arg), TOPMed rs1169046984, gnomAD rs1169046984, Uncertain significance, not provided
- G53R (p.Gly53Arg), rs2034119580, ClinGen CA398754209, ClinVar RCV003011346, AlphaMissense 0.28, MetaLR 0.93, Uncertain significance, not provided
- G53W (p.Gly53Trp), rs2034119580, Ensembl rs2034119580, ClinGen CA398754211, ClinVar RCV001258209, AlphaMissense 0.28, MetaLR 0.93, Uncertain significance, Renal cysts and diabetes syndrome; Maturity-onset diabetes of the young
- A54P (p.Ala54Pro), ExAC rs776801574, gnomAD rs776801574
- E55K (p.Glu55Lys), rs747360527, ExAC rs747360527, TOPMed rs747360527, gnomAD rs747360527, CADD 22.10, PolyPhen-2 0.01, Uncertain significance, HNF1B-related disorder
- D57E (p.Asp57Glu), TOPMed rs1242784159, gnomAD rs1242784159, CADD 17.90, PolyPhen-2 0.25, Uncertain significance, Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal
- D57N (p.Asp57Asn), gnomAD rs2034119029
- P60L (p.Pro60Leu), ExAC rs778234238, TOPMed rs778234238, gnomAD rs778234238, CADD 28.40, PolyPhen-2 0.46
- P60R (p.Pro60Arg), ExAC rs778234238, TOPMed rs778234238, gnomAD rs778234238, CADD 27.70, PolyPhen-2 0.47
- P60S (p.Pro60Ser), 1000Genomes rs551134668, ExAC rs551134668, TOPMed rs551134668, gnomAD rs551134668, CADD 23.40, PolyPhen-2 0.33, Uncertain significance, not provided
- V61G (p.Val61Gly), rs147816724, ClinGen CA8519137, ClinVar RCV000440404, ClinVar RCV000664148, CADD 22.90, PolyPhen-2 0.01, Conflicting interpretations, Monogenic diabetes; not specified; Maturity-onset diabetes of the young
- V61I (p.Val61Ile), ExAC rs754482958, TOPMed rs754482958, gnomAD rs754482958, CADD 21.70, PolyPhen-2 0.11, Uncertain significance, HNF1B-related disorder
- F62C (p.Phe62Cys), ExAC rs779843436, gnomAD rs779843436, CADD 26.90, PolyPhen-2 1.00
- F62L (p.Phe62Leu), Ensembl rs2034118026
- F62Y (p.Phe62Tyr), ExAC rs779843436, gnomAD rs779843436, CADD 24.90, PolyPhen-2 0.99
- H63Y (p.His63Tyr), ExAC rs756043181, gnomAD rs756043181, CADD 22.80, PolyPhen-2 0.21, Uncertain significance, not provided
- T64A (p.Thr64Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T64S (p.Thr64Ser), TOPMed rs1213958093, gnomAD rs1213958093, CADD 22.40, PolyPhen-2 0.28, Uncertain significance, Renal cysts and diabetes syndrome; Nonpapillary renal cell carcinoma; Type 2 dia
- L65F (p.Leu65Phe), gnomAD rs1336990799, CADD 26.80, PolyPhen-2 0.77, Uncertain significance, Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal
- N67K (p.Asn67Lys), TOPMed rs1404879910, gnomAD rs1404879910, CADD 24.40, PolyPhen-2 0.88
- N67S (p.Asn67Ser), Ensembl rs2034117204
- N67Y (p.Asn67Tyr), TOPMed rs1445076741, CADD 31.00, PolyPhen-2 0.96
- G68A (p.Gly68Ala), TOPMed rs1192274088, gnomAD rs1192274088, CADD 23.10
- G68R (p.Gly68Arg), rs767576616, ClinGen CA8519133, ClinVar RCV001248884, ClinVar RCV002570390, CADD 28.60, PolyPhen-2 0.98, Uncertain significance, not provided; Maturity-onset diabetes of the young
- H69Y (p.His69Tyr), gnomAD rs2034116714, CADD 22.90, PolyPhen-2 0.33, Uncertain significance, not provided
- A70S (p.Ala70Ser), ExAC rs761609163, TOPMed rs761609163, gnomAD rs761609163, CADD 16.00, PolyPhen-2 0.01
- A70T (p.Ala70Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A70V (p.Ala70Val), ExAC rs752853989, gnomAD rs752853989, CADD 23.20, PolyPhen-2 0.00
- K71N (p.Lys71Asn), rs1442869406, gnomAD rs1442869406, CADD 24.00, PolyPhen-2 0.45, Variant assessed as somatic; moderate impact.
- G72D (p.Gly72Asp), gnomAD rs1384611067, CADD 24.80, PolyPhen-2 1.00
- G72V (p.Gly72Val), gnomAD rs1384611067
- R73C (p.Arg73Cys), Ensembl rs2034115909, CADD 32.00, PolyPhen-2 0.54, Uncertain significance, not provided
- R73L (p.Arg73Leu), rs2034115814, TOPMed rs2034115814, gnomAD rs2034115814, ClinGen CA398753777, CADD 24.70, PolyPhen-2 0.10, Uncertain significance, not provided
- L74* (p.Leu74Ter), rs193922486, TOPMed rs193922486, ClinGen CA214355, ClinVar RCV000030526, AlphaMissense 0.38, MetaLR 0.95, Pathogenic
- L74F (p.Leu74Phe), TOPMed rs1184510592, gnomAD rs1184510592, CADD 17.70, PolyPhen-2 0.35
- L74W (p.Leu74Trp), rs193922486, ClinGen CA398753761, ClinVar RCV002464978, ClinVar RCV004753563, AlphaMissense 0.38, MetaLR 0.95, Pathogenic, Maturity-onset diabetes of the young
- S75F (p.Ser75Phe), gnomAD rs1425769671, CADD 32.00, PolyPhen-2 0.72
- G76C (p.Gly76Cys), rs144425830, ClinGen CA200314, ClinVar RCV000173138, ClinVar RCV000369522, CADD 31.00, PolyPhen-2 1.00, Conflicting interpretations, not specified; not provided; Nonpapillary renal cell carcinoma
- G76D (p.Gly76Asp), TOPMed rs972535515, CADD 23.90, PolyPhen-2 1.00, Uncertain significance, in RCAD
- G76S (p.Gly76Ser), 1000Genomes rs144425830, ESP rs144425830, ExAC rs144425830, TOPMed rs144425830, Likely benign, in RCAD
- D77E (p.Asp77Glu), rs760448993, TOPMed rs760448993, gnomAD rs760448993, ClinGen CA290293155, CADD 24.30, PolyPhen-2 1.00, Conflicting interpretations, not provided; Type 2 diabetes mellitus; Nonpapillary renal cell carcinoma
- D77G (p.Asp77Gly), Ensembl rs1399320508
- D77H (p.Asp77His), gnomAD rs1480809337, CADD 29.30, PolyPhen-2 1.00
- E78* (p.Glu78Ter), rs2511850923, ClinGen CA398753654, ClinVar RCV000787244, ClinVar RCV001029833, CADD 38.00, Pathogenic
- E78A (p.Glu78Ala), rs2511850894, ClinGen CA398753644, ClinVar RCV003442740, Uncertain significance, not provided
- E78D (p.Glu78Asp), rs2511850885, ClinGen CA398753634, ClinVar RCV000787242, Likely pathogenic, Renal cysts and diabetes syndrome
- G79A (p.Gly79Ala), ExAC rs759636901, TOPMed rs759636901, gnomAD rs759636901, CADD 23.70, PolyPhen-2 1.00
- G79D (p.Gly79Asp), ExAC rs759636901, TOPMed rs759636901, gnomAD rs759636901, CADD 24.10, PolyPhen-2 1.00
- G79S (p.Gly79Ser), Ensembl rs2147599148
- G79V (p.Gly79Val), ExAC rs759636901, TOPMed rs759636901, gnomAD rs759636901, CADD 24.10, PolyPhen-2 1.00
- S80F (p.Ser80Phe), rs942582464, Ensembl rs942582464, ClinGen CA290293142, ClinVar RCV001759236, CADD 29.10, PolyPhen-2 0.72, Uncertain significance, not provided
- E81* (p.Glu81Ter), rs2034113963, ClinGen CA398753594, ClinVar RCV001262003, ClinVar RCV002465859, Pathogenic
- E81D (p.Glu81Asp), TOPMed rs2034113846, gnomAD rs2034113846, CADD 16.40
- D82H (p.Asp82His), 1000Genomes rs140562402, ESP rs140562402, ExAC rs140562402, TOPMed rs140562402, Likely benign
- D82N (p.Asp82Asn), rs140562402, 1000Genomes rs140562402, ESP rs140562402, ExAC rs140562402, CADD 28.80, PolyPhen-2 0.53, Conflicting interpretations, Monogenic diabetes; not specified; not provided
- G83D (p.Gly83Asp), rs2511850713, ClinGen CA398753543, ClinVar RCV000787240, Likely pathogenic, Renal cysts and diabetes syndrome
- D85G (p.Asp85Gly), rs984116301, ClinGen CA290293133, ClinVar RCV000730141, ClinVar RCV002249441, AlphaMissense 0.75, MetaLR 0.92, Uncertain significance, not specified; not provided
- D85H (p.Asp85His), ExAC rs772653373, gnomAD rs772653373, CADD 29.40, PolyPhen-2 0.86
- D85N (p.Asp85Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y86H (p.Tyr86His), ExAC rs748645433
- D87N (p.Asp87Asn), TOPMed rs1391196377, gnomAD rs1391196377, CADD 23.40, PolyPhen-2 0.16
- T88A (p.Thr88Ala), rs1555833051, Ensembl rs1555833051, ClinGen CA398753475, ClinVar RCV000664147, AlphaMissense 0.24, MetaLR 0.90, Uncertain significance/Uncertain risk allele, Monogenic diabetes; Maturity-onset diabetes of the young
- T88K (p.Thr88Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P89L (p.Pro89Leu), ExAC rs779455046, TOPMed rs779455046, gnomAD rs779455046, CADD 32.00, PolyPhen-2 0.94
- P90T (p.Pro90Thr), rs772315985, ClinGen CA290293121, ClinVar RCV001127841, ClinVar RCV002465832, CADD 28.50, PolyPhen-2 0.66, Conflicting interpretations, Maturity-onset diabetes of the young; Renal cysts and diabetes syndrome
- I91V (p.Ile91Val), rs1204310134, ClinGen CA398753422, ClinVar RCV004344291, ClinVar RCV006561489, CADD 24.20, PolyPhen-2 0.03, Uncertain significance, Maturity-onset diabetes of the young; not provided
- L92F (p.Leu92Phe), rs2147598858, ClinGen CA398753400, ClinVar RCV000787236, AlphaMissense 0.50, MetaLR 0.95, Likely pathogenic, Renal cysts and diabetes syndrome
- L92V (p.Leu92Val), Ensembl rs2147598858
- K93Q (p.Lys93Gln), gnomAD rs1489207973, CADD 23.50, PolyPhen-2 0.42
- E94* (p.Glu94Ter), rs1405279061, ClinGen CA398753336, ClinVar RCV002776551, AlphaMissense 0.95, MetaLR 0.96, Pathogenic
- E94G (p.Glu94Gly), rs2511850235, ClinGen CA398753320, ClinVar RCV003312387, CADD 26.80, PolyPhen-2 0.00, Uncertain significance, not provided
- E94K (p.Glu94Lys), TOPMed rs1405279061, gnomAD rs1405279061, AlphaMissense 0.95, MetaLR 0.96
- A97S (p.Ala97Ser), TOPMed rs1255423796
- A97V (p.Ala97Val), NCI-TCGA TCGA novel, CADD 23.80, PolyPhen-2 0.06, Variant assessed as somatic; moderate impact.
- L98R (p.Leu98Arg), rs2034111132, ClinGen CA398753237, ClinVar RCV002938842, Ensembl rs2034111132, CADD 25.40, PolyPhen-2 0.03, Uncertain significance, not provided
- L98V (p.Leu98Val), TOPMed rs1474915634
- T100A (p.Thr100Ala), rs1568675935, ClinGen CA398753195, ClinVar RCV000729928, TOPMed rs1568675935, AlphaMissense 0.26, MetaLR 0.93, Uncertain significance, not provided
- T100S (p.Thr100Ser), rs1568675935, ClinGen CA398753191, ClinVar RCV002465957, TOPMed rs1568675935, AlphaMissense 0.26, MetaLR 0.93, Uncertain risk allele, Maturity-onset diabetes of the young
- E101* (p.Glu101Ter), rs121918671, ExAC rs121918671, gnomAD rs121918671, ClinGen CA122599, AlphaMissense 0.23, MetaLR 0.94, Pathogenic
- E101Q (p.Glu101Gln), rs121918671, ClinGen CA8519119, ClinVar RCV002895553, ExAC rs121918671, AlphaMissense 0.23, MetaLR 0.94, Uncertain significance, not provided
- E102A (p.Glu102Ala), rs982165538, TOPMed rs982165538, gnomAD rs982165538, ClinGen CA290293071, CADD 31.00, PolyPhen-2 0.61, Uncertain significance, Renal cysts and diabetes syndrome; Nonpapillary renal cell carcinoma; Type 2 dia
- A103V (p.Ala103Val), gnomAD rs1253702848, CADD 29.70, PolyPhen-2 0.59, Uncertain significance, not provided
- A104T (p.Ala104Thr), gnomAD rs1490161010, CADD 25.00, PolyPhen-2 0.33
- A104V (p.Ala104Val), rs2511849835, ClinGen CA398753113, ClinVar RCV002320474, CADD 22.50, PolyPhen-2 0.02, Uncertain significance, Maturity-onset diabetes of the young
- E105D (p.Glu105Asp), gnomAD rs1347858100, CADD 24.00, PolyPhen-2 0.99, Uncertain significance, Renal cysts and diabetes syndrome; Type 2 diabetes mellitus; Nonpapillary renal
- E105G (p.Glu105Gly), rs375625110, ClinGen CA8519116, ClinVar RCV000993277, ClinVar RCV002505508, CADD 32.00, PolyPhen-2 1.00, Conflicting interpretations, Nonpapillary renal cell carcinoma; Renal cysts and diabetes syndrome; Type 2 dia
- E105K (p.Glu105Lys), rs199572129, 1000Genomes rs199572129, ExAC rs199572129, TOPMed rs199572129, CADD 24.40, PolyPhen-2 1.00, Conflicting interpretations, not specified; not provided; Renal cysts and diabetes syndrome
- R107Q (p.Arg107Gln), rs970826378, gnomAD rs970826378, ClinGen CA290293048, ClinVar RCV003680791, CADD 29.10, PolyPhen-2 1.00, Uncertain significance, not provided
- E109K (p.Glu109Lys), rs757044850, ClinGen CA398753017, ClinVar RCV000591875, ClinVar RCV005645107, AlphaMissense 0.33, MetaLR 0.93, Uncertain significance, not provided; Renal cysts and diabetes syndrome
- E109Q (p.Glu109Gln), rs757044850, ExAC rs757044850, gnomAD rs757044850, ClinGen CA8519115, AlphaMissense 0.33, MetaLR 0.93, Uncertain risk allele, Maturity-onset diabetes of the young
- V110G (p.Val110Gly), rs894213416, ClinGen CA290293036, ClinVar RCV000787233, UniProt VAR 046015, AlphaMissense 0.94, MetaLR 0.98, Likely pathogenic, Renal cysts and diabetes syndrome
- V110M (p.Val110Met), ExAC rs751498987, gnomAD rs751498987, CADD 28.40, PolyPhen-2 0.78
- D111G (p.Asp111Gly), rs1311605355, ClinGen CA398752970, ClinVar RCV002618481, ClinVar RCV003403877, CADD 32.00, PolyPhen-2 0.66, Uncertain significance, Renal cysts and diabetes syndrome; Nonpapillary renal cell carcinoma; Type 2 dia
- R112P (p.Arg112Pro), rs953274911, ClinGen CA398752937, ClinVar RCV000787232, UniProt VAR 046016, AlphaMissense 0.11, MetaLR 0.84, Pathogenic, Renal cysts and diabetes syndrome
- R112Q (p.Arg112Gln), TOPMed rs953274911, gnomAD rs953274911, AlphaMissense 0.11, MetaLR 0.84
- M113I (p.Met113Ile), rs764079701, ClinGen CA8519113, ClinVar RCV000732964, ClinVar RCV002465765, CADD 23.70, PolyPhen-2 0.03, Uncertain significance/Uncertain risk allele, not provided; Maturity-onset diabetes of the young
- S115N (p.Ser115Asn), rs193922487, Ensembl rs193922487, ClinGen CA214357, ClinVar RCV000030527, AlphaMissense 0.13, MetaLR 0.90, Conflicting interpretations, Maturity-onset diabetes of the young; Renal cysts and diabetes syndrome
- D117V (p.Asp117Val), TOPMed rs914905499, CADD 29.90, PolyPhen-2 1.00
- P118A (p.Pro118Ala), rs745356532, ClinGen CA398751745, ClinVar RCV003988555, ExAC rs745356532, CADD 23.90, PolyPhen-2 0.44, Uncertain significance, not specified
- P118S (p.Pro118Ser), ExAC rs745356532, gnomAD rs745356532, CADD 23.00, PolyPhen-2 0.14, Uncertain significance
- P118T (p.Pro118Thr), ExAC rs745356532, gnomAD rs745356532, CADD 26.30, PolyPhen-2 0.75, Uncertain significance
- W119* (p.Trp119Ter), rs2511830005, ClinGen CA398751737, ClinVar RCV000787223, Pathogenic
- R120G (p.Arg120Gly), gnomAD rs2033932710, CADD 32.00
- A122T (p.Ala122Thr), rs1568670778, Ensembl rs1568670778, ClinGen CA398751718, ClinVar RCV000731660, AlphaMissense 0.98, MetaLR 0.97, Uncertain significance/Uncertain risk allele, not provided; Maturity-onset diabetes of the young
- M124I (p.Met124Ile), rs2511829901, ClinGen CA398751698, ClinVar RCV000787222, NCI-TCGA TCGA novel, Likely pathogenic, Renal cysts and diabetes syndrome
- I125M (p.Ile125Met), ExAC rs770550658, TOPMed rs770550658, gnomAD rs770550658, Likely benign
- I125N (p.Ile125Asn), rs2147575564, Ensembl rs2147575564, ClinGen CA398751692, ClinVar RCV001665489, AlphaMissense 1.00, MetaLR 0.97, Uncertain significance, not provided
- I125T (p.Ile125Thr), rs2147575564, ClinGen CA398751691, ClinVar RCV000787221, AlphaMissense 1.00, MetaLR 0.97, Pathogenic, Renal cysts and diabetes syndrome
- K126E (p.Lys126Glu), rs2511829849, ClinGen CA398751687, ClinVar RCV003129231, Uncertain significance, not provided
- Y128F (p.Tyr128Phe), Ensembl rs2033932056
- M129I (p.Met129Ile), TOPMed rs2033931848, gnomAD rs2033931848, CADD 25.30, PolyPhen-2 0.98
- Q131* (p.Gln131Ter), rs2511829685, ClinGen CA398751625, ClinVar RCV000787220, Pathogenic
- H132L (p.His132Leu), rs2511829635, ClinVar RCV004566475, Likely pathogenic, Renal cysts and diabetes syndrome
- H132P (p.His132Pro), rs2511829635, ClinGen CA398751611, ClinVar RCV000787218, Likely pathogenic, Renal cysts and diabetes syndrome
- H132Q (p.His132Gln), Ensembl rs1598848830
- H132R (p.His132Arg), rs2511829635, ClinGen CA398751609, ClinVar RCV003148509, Likely pathogenic, Renal cysts and diabetes syndrome
- N133S (p.Asn133Ser), rs2511829602, ClinGen CA398751597, ClinVar RCV000787217, Pathogenic, Renal cysts and diabetes syndrome
- I134N (p.Ile134Asn), rs2147575462, ClinGen CA398751583, ClinVar RCV001977148, Ensembl rs2147575462, AlphaMissense 1.00, MetaLR 0.97, Uncertain significance, not provided
- Q136* (p.Gln136Ter), rs2511829513, ClinGen CA398751565, ClinVar RCV000787214, ClinVar RCV002535750, Pathogenic, in RCAD
- Q136E (p.Gln136Glu), rs2511829513, ClinGen CA398751567, ClinVar RCV000787215, UniProt VAR 046017, Pathogenic, Renal cysts and diabetes syndrome
- R137K (p.Arg137Lys), rs2147575425, ClinGen CA398751552, ClinVar RCV002052103, Ensembl rs2147575425, CADD 26.70, PolyPhen-2 0.99, Uncertain significance, Type 2 diabetes mellitus
- V139G (p.Val139Gly), rs2511829485, ClinGen CA398751523, ClinVar RCV003579993, Uncertain significance, not provided
- D141N (p.Asp141Asn), Ensembl rs866277746, CADD 27.20, PolyPhen-2 1.00, Uncertain significance, not specified
- G144S (p.Gly144Ser), rs374126219, ESP rs374126219, ExAC rs374126219, TOPMed rs374126219, CADD 27.30, PolyPhen-2 1.00, Uncertain significance, not provided
- G144V (p.Gly144Val), TOPMed rs2033930818
Public HNF1B analysis runs
- HNF1B analysis run — HNF1B (996 variants) — completed 2026-08-19