CDKN1B (P46527) variants and mutations
CDKN1B (also known as P46527) is a human protein-coding gene encoding a cyclin-dependent kinase inhibitor 1B protein. It restrains cell-cycle progression by inhibiting cyclin-CDK complexes and integrates mitogenic and antiproliferative signals. Germline loss-of-function variants cause MEN4, while reduced expression or mislocalization is common in cancer. This analysis covers 924 CDKN1B variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes multiple endocrine neoplasia type 4, prostate carcinoma, and Inherited cancer-predisposing syndrome. Example CDKN1B variants include M1I, M1T, and M1V.
Variant analysis overview
- Gene: CDKN1B
- Protein: P46527
- UniProt accession: P46527
- Organism: Homo sapiens
- Variants analyzed: 924
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 738 unspecified-consequence records; 127 synonymous variants; 20 frameshift variants; 34 missense variants; 2 splice-region variants; 3 stop-gained variants; 5 in-frame deletions; 1 in-frame insertions; 1 stop lost
- Prediction scores: 719 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: multiple endocrine neoplasia type 4, prostate carcinoma, Inherited cancer-predisposing syndrome, hereditary neoplastic syndrome, thyroid gland carcinoma, neurodegenerative disease, pituitary gland adenoma, thyroid cancer, type 2 diabetes mellitus, prostate adenocarcinoma, primary hyperparathyroidism, breast adenocarcinoma.
Protein structure and variant hotspots
- Protein features: 8 post-translational modification sites.
- PTM context: 43 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 CDKN1B variants
Examples include M1I, M1T, M1V, S2L, N3D, N3K, N3N, V4A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs756190836, ClinGen CA6457360, ClinVar RCV000551866, ClinVar RCV002377114, MetaLR 0.81, MetaSVM 0.81, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Multiple endocrine neopla
- M1T (p.Met1Thr), rs1946485229, ClinGen CA383967816, ClinVar RCV003377517, MetaLR 0.79, MetaSVM 0.62, Uncertain significance, Hereditary cancer-predisposing syndrome
- M1V (p.Met1Val), rs1946485126, ClinGen CA383967809, ClinVar RCV001231385, MetaLR 0.80, MetaSVM 0.78, Uncertain significance, Multiple endocrine neoplasia type 4
- S2L (p.Ser2Leu), rs2136355327, ClinGen CA383967852, cosmic curated COSV57430, ClinVar RCV001933141, REVEL 0.68, CADD 29.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- N3D (p.Asn3Asp), rs1348090532, ClinGen CA383967862, cosmic curated COSV99963, ClinVar RCV000570849, REVEL 0.21, CADD 22.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- N3K (p.Asn3Lys), rs1411622351, ClinGen CA383967882, ClinVar RCV002006805, ClinVar RCV004947031, REVEL 0.32, CADD 23.60, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- N3N (p.Asn3Asn), rs1411622351, gnomAD 12-12717848-C-T, CADD 13.60
- V4A (p.Val4Ala), rs1946485501, ClinGen CA383967901, ClinVar RCV001211462, Ensembl rs1946485501, AlphaMissense 0.80, MetaLR 0.57, Uncertain significance, Multiple endocrine neoplasia type 4
- V4C (p.Val4Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V4L (p.Val4Leu), rs780124638, ClinGen CA6457361, ClinVar RCV001232438, ClinVar RCV004951381, REVEL 0.56, CADD 26.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- V4M (p.Val4Met), rs780124638, ClinGen CA383967890, ClinVar RCV002430946, ClinVar RCV005098158, REVEL 0.59, CADD 27.70, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- V4V (p.Val4Val), rs1555085477, gnomAD 12-12717851-G-A, CADD 13.20
- R5* (p.Arg5Ter), rs1349668409, ClinGen CA383967913, cosmic curated COSV10633, ClinVar RCV000782205, AlphaMissense 0.75, MetaLR 0.71, Pathogenic
- R5G (p.Arg5Gly), rs1349668409, ClinGen CA383967910, ClinVar RCV001358989, ClinVar RCV003339614, AlphaMissense 0.75, MetaLR 0.71, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- R5Q (p.Arg5Gln), rs1408164050, ClinGen CA383967915, cosmic curated COSV10506, ClinVar RCV001040473, REVEL 0.38, CADD 32.00, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- R5R (p.Arg5Arg), gnomAD 12-12717852-C-A, CADD 13.60
- V6A (p.Val6Ala), rs1946485641, ClinGen CA383967932, ClinVar RCV001058043, Ensembl rs1946485641, AlphaMissense 0.84, MetaLR 0.43, Uncertain significance, Multiple endocrine neoplasia type 4
- V6L (p.Val6Leu), rs2136355356, ClinGen CA383967925, ClinVar RCV001993415, ClinVar RCV005792248, REVEL 0.13, AlphaMissense 0.47, Uncertain significance, Hereditary cancer-predisposing syndrome
- V6M (p.Val6Met), rs2136355356, ClinGen CA383967922, cosmic curated COSV10506, ClinVar RCV002024999, AlphaMissense 0.47, MetaLR 0.49, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- V6S (p.Val6Ser), gnomAD 12-12717850-TGCGA, CADD 32.00
- V6G (p.Val6Gly), gnomAD 12-12717856-T-G, REVEL 0.67, CADD 29.30
- S7C (p.Ser7Cys), rs368157535, ClinGen CA233059551, cosmic curated COSV57429, ClinVar RCV000524886, REVEL 0.66, CADD 27.90, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- S7F (p.Ser7Phe), gnomAD 12-12717859-C-T, REVEL 0.62, CADD 28.80
- N8* (p.Asn8Ter), rs2136355372, ClinGen CA2573147857, ClinVar RCV001923787, ClinVar RCV002425256, CADD 30.00, Pathogenic
- N8D (p.Asn8Asp), TOPMed rs1946485763, Uncertain significance, Hereditary cancer-predisposing syndrome
- N8Y (p.Asn8Tyr), rs1946485763, ClinGen CA383967964, ClinVar RCV002302394, ClinVar RCV005535328, AlphaMissense 0.31, MetaLR 0.42, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- N8G (p.Asn8Gly), gnomAD 12-12717860-TAACG, CADD 32.00
- N8N (p.Asn8Asn), rs371308246, gnomAD 12-12717863-C-T, CADD 13.70
- G9A (p.Gly9Ala), gnomAD rs1946485926, REVEL 0.48, CADD 26.30, Uncertain significance
- G9E (p.Gly9Glu), rs1946485926, ClinGen CA383967991, ClinVar RCV001886472, gnomAD rs1946485926, REVEL 0.50, CADD 27.40, Uncertain significance, Multiple endocrine neoplasia type 4
- G9R (p.Gly9Arg), rs755225286, ClinGen CA6457363, ClinVar RCV000460935, ClinVar RCV000782207, REVEL 0.58, AlphaMissense 0.92, Uncertain significance, Multiple endocrine neoplasia type 4
- G9W (p.Gly9Trp), rs755225286, ClinGen CA383967987, NCI-TCGA Cosmic COSV5743, cosmic curated COSV57430, AlphaMissense 0.92, MetaLR 0.75, Uncertain significance, Multiple endocrine neoplasia type 4
- G9G (p.Gly9Gly), rs1060503869, gnomAD 12-12717866-G-A, CADD 14.40
- S10G (p.Ser10Gly), Ensembl rs2136355385
- S10N (p.Ser10Asn), rs1555085482, ClinGen CA383968018, ClinVar RCV000528696, ClinVar RCV001017897, AlphaMissense 0.91, MetaLR 0.71, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- S10R (p.Ser10Arg), rs990433180, ClinGen CA383968033, ClinVar RCV001978655, ClinVar RCV002324379, AlphaMissense 0.99, MetaLR 0.69, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- S10T (p.Ser10Thr), rs1555085482, ClinGen CA383968022, ClinVar RCV001058315, ClinVar RCV003153914, AlphaMissense 0.91, MetaLR 0.71, Uncertain significance, Multiple endocrine neoplasia type 4; not provided
- S10E (p.Ser10Glu), gnomAD 12-12717863-C-CG, CADD 32.00
- S10S (p.Ser10Ser), rs990433180, gnomAD 12-12717869-C-T, AlphaMissense 0.99, MetaLR 0.69
- P11A (p.Pro11Ala), rs779193240, ClinGen CA383968035, ClinVar RCV000798195, ClinVar RCV005532760, AlphaMissense 0.77, MetaLR 0.73, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- P11L (p.Pro11Leu), rs748543504, NCI-TCGA TCGA novel, ClinGen CA383968045, ClinVar RCV001304315, REVEL 0.73, CADD 28.10, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- P11R (p.Pro11Arg), rs748543504, ClinGen CA6457365, ClinVar RCV002454678, ClinVar RCV005096232, REVEL 0.68, CADD 26.70, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- P11S (p.Pro11Ser), rs779193240, ClinGen CA6457364, cosmic curated COSV57429, ClinVar RCV000466839, REVEL 0.57, AlphaMissense 0.77, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Ovarian cancer; not provided
- P11P (p.Pro11Pro), gnomAD 12-12717872-T-C, CADD 13.20
- S12G (p.Ser12Gly), rs1592280717, ClinGen CA383968052, ClinVar RCV001020457, ClinVar RCV001222278, REVEL 0.30, CADD 23.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- S12I (p.Ser12Ile), rs775772074, ClinGen CA233059580, ClinVar RCV000542106, ClinVar RCV001020692, REVEL 0.21, AlphaMissense 0.59, Conflicting interpretations, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome; no
- S12N (p.Ser12Asn), rs775772074, ClinGen CA6457366, cosmic curated COSV99963, ClinVar RCV000814993, REVEL 0.25, AlphaMissense 0.59, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Multiple endocrine neopla
- S12R (p.Ser12Arg), rs778425357, ClinGen CA383968061, ClinVar RCV003339039, REVEL 0.31, CADD 23.30, Uncertain significance, Hereditary cancer-predisposing syndrome
- S12T (p.Ser12Thr), rs775772074, ClinGen CA383968055, ClinVar RCV001312831, ClinVar RCV005532931, AlphaMissense 0.59, MetaLR 0.33, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- S12S (p.Ser12Ser), rs778425357, gnomAD 12-12717875-C-T, CADD 14.50
- L13R (p.Leu13Arg), rs1946486449, ClinGen CA383968080, ClinVar RCV001319536, ClinVar RCV002357143, REVEL 0.79, CADD 31.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- L13L (p.Leu13Leu), rs1946486404, gnomAD 12-12717876-C-T, CADD 11.80
- E14G (p.Glu14Gly), rs1467549866, ClinGen CA383968104, ClinVar RCV001022034, ClinVar RCV003619736, REVEL 0.75, CADD 32.00, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- E14K (p.Glu14Lys), rs2497403775, ClinGen CA383968088, ClinVar RCV003620426, REVEL 0.73, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- E14V (p.Glu14Val), gnomAD 12-12717880-A-T, REVEL 0.80, CADD 32.00
- E14E (p.Glu14Glu), rs747456770, gnomAD 12-12717881-G-A, CADD 13.30
- R15Q (p.Arg15Gln), TOPMed rs1946486690
- R15W (p.Arg15Trp), rs2066828, ClinGen CA6457369, ClinVar RCV000540605, ClinVar RCV001022424, REVEL 0.60, CADD 28.00, Uncertain significance, not provided; Multiple endocrine neoplasia type 4; Hereditary cancer-predisposin
- R15R (p.Arg15Arg), rs775058606, gnomAD 12-12717884-G-C, CADD 13.90
- M16I (p.Met16Ile), rs1946486852, ClinGen CA383968146, ClinVar RCV004516444, ClinVar RCV005100458, REVEL 0.20, CADD 22.70, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- M16R (p.Met16Arg), TOPMed rs1411029555, gnomAD rs1411029555, REVEL 0.46, CADD 23.10
- M16V (p.Met16Val), rs1162081170, ClinGen CA383968129, ClinVar RCV001321786, ClinVar RCV004609763, REVEL 0.26, CADD 22.40, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4; no
- D17E (p.Asp17Glu), rs552533838, ClinGen CA383968173, cosmic curated COSV57429, ClinVar RCV000994851, REVEL 0.20, CADD 19.10, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Multiple endocrine neopla
- D17H (p.Asp17His), Ensembl rs2136355436
- D17G (p.Asp17Gly), gnomAD 12-12717889-A-G, REVEL 0.42, CADD 31.00
- D17D (p.Asp17Asp), rs552533838, gnomAD 12-12717890-C-T, CADD 13.80
- A18D (p.Ala18Asp), Ensembl rs1277429969, Uncertain significance
- A18G (p.Ala18Gly), rs1277429969, ClinGen CA383968192, ClinVar RCV002347252, ClinVar RCV003096723, REVEL 0.25, CADD 22.10, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- A18T (p.Ala18Thr), gnomAD rs1946486987, REVEL 0.41, CADD 23.30
- A18V (p.Ala18Val), rs1277429969, ClinGen CA383968195, ClinVar RCV002481130, ClinVar RCV002571547, REVEL 0.42, CADD 25.20, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4; no
- A18A (p.Ala18Ala), rs151027466, gnomAD 12-12717893-C-T, CADD 15.70
- R19G (p.Arg19Gly), rs1555085496, ClinGen CA383968202, ClinVar RCV000570078, ClinVar RCV003619693, AlphaMissense 0.72, MetaLR 0.65, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- R19K (p.Arg19Lys), cosmic curated COSV10584, Ensembl rs1946487134, REVEL 0.42, CADD 24.80, Uncertain significance, Hereditary cancer-predisposing syndrome
- R19T (p.Arg19Thr), Ensembl rs1946487134
- R19P (p.Arg19Pro), gnomAD 12-12717890-CGCCA, CADD 32.00
- R19W (p.Arg19Trp), gnomAD 12-12717894-A-T, REVEL 0.61, CADD 23.30
- R19S (p.Arg19Ser), gnomAD 12-12717896-G-C, REVEL 0.63, CADD 20.60
- R19R (p.Arg19Arg), rs1946487176, gnomAD 12-12717896-G-A, CADD 9.81
- Q20* (p.Gln20Ter), rs1946487230, ClinGen CA383968213, NCI-TCGA Cosmic COSV5743, cosmic curated COSV57431, CADD 37.00, Pathogenic
- Q20H (p.Gln20His), rs1369715485, ClinGen CA383968229, ClinVar RCV002046293, ClinVar RCV006372591, AlphaMissense 0.33, MetaLR 0.53, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- Q20K (p.Gln20Lys), Ensembl rs1946487230, Pathogenic
- Q20R (p.Gln20Arg), gnomAD rs1169150313, REVEL 0.16, CADD 21.90
- Q20P (p.Gln20Pro), gnomAD 12-12717898-A-C, REVEL 0.13, CADD 21.70
- A21G (p.Ala21Gly), rs1229515408, ClinGen CA383968251, ClinVar RCV003177198, AlphaMissense 0.14, MetaLR 0.43, Uncertain significance, Hereditary cancer-predisposing syndrome
- A21T (p.Ala21Thr), rs1422774752, ClinGen CA383968237, ClinVar RCV002353850, ClinVar RCV003509726, REVEL 0.17, CADD 19.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- A21V (p.Ala21Val), rs1229515408, ClinGen CA383968250, cosmic curated COSV57429, ClinVar RCV002353953, REVEL 0.26, AlphaMissense 0.14, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- A21A (p.Ala21Ala), rs1427650079, gnomAD 12-12717902-G-A, CADD 12.10
- E22* (p.Glu22Ter), NCI-TCGA Cosmic COSV5742, cosmic curated COSV57429, CADD 40.00, Variant assessed as somatic; high impact.
- E22K (p.Glu22Lys), rs2136355461, ClinGen CA383968255, ClinVar RCV002046722, Ensembl rs2136355461, REVEL 0.41, AlphaMissense 0.36, Uncertain significance, Multiple endocrine neoplasia type 4
- E22Q (p.Glu22Gln), rs2136355461, ClinGen CA383968258, ClinVar RCV001958210, ClinVar RCV002361284, AlphaMissense 0.36, MetaLR 0.47, Uncertain significance, not provided; Multiple endocrine neoplasia type 4; Hereditary cancer-predisposin
- H23L (p.His23Leu), rs1946487581, ClinGen CA383968303, ClinVar RCV004516452, REVEL 0.23, CADD 24.20, Uncertain significance, Hereditary cancer-predisposing syndrome
- H23N (p.His23Asn), Ensembl rs1946487548, Uncertain significance
- H23Q (p.His23Gln), rs1946487615, ClinGen CA383968306, ClinVar RCV001218225, Ensembl rs1946487615, AlphaMissense 0.22, MetaLR 0.33, Uncertain significance, Multiple endocrine neoplasia type 4
- H23R (p.His23Arg), rs1946487581, ClinGen CA383968300, ClinVar RCV002040687, ClinVar RCV005792282, REVEL 0.26, CADD 23.90, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- H23Y (p.His23Tyr), rs1946487548, ClinGen CA383968295, ClinVar RCV001235468, ClinVar RCV005306352, REVEL 0.18, CADD 19.40, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- P24L (p.Pro24Leu), rs2497403916, ClinGen CA383968326, ClinVar RCV002370844, ClinVar RCV006469769, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- P24R (p.Pro24Arg), rs2497403916, ClinGen CA383968323, ClinVar RCV003065751, ClinVar RCV006381806, REVEL 0.54, CADD 27.70, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- P24S (p.Pro24Ser), rs2136355480, ClinGen CA383968315, ClinVar RCV001360029, ClinVar RCV002368162, AlphaMissense 0.27, MetaLR 0.62, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- P24T (p.Pro24Thr), rs2136355480, ClinGen CA383968312, ClinVar RCV003509024, AlphaMissense 0.27, MetaLR 0.62, Uncertain significance, Multiple endocrine neoplasia type 4
- P24P (p.Pro24Pro), rs1336379841, gnomAD 12-12717911-C-T, CADD 13.80
- K25S (p.Lys25Ser), gnomAD 12-12717911-CA-C, CADD 32.00
- K25K (p.Lys25Lys), rs367611328, gnomAD 12-12717914-G-A, CADD 11.90
- P26L (p.Pro26Leu), rs2136355491, ClinGen CA383968382, cosmic curated COSV57429, ClinVar RCV001925293, AlphaMissense 0.56, MetaLR 0.74, Uncertain significance, Hereditary cancer-predisposing syndrome
- P26S (p.Pro26Ser), rs2136355486, ClinGen CA383968371, ClinVar RCV002933269, ClinVar RCV005535455, REVEL 0.36, CADD 26.30, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- P26P (p.Pro26Pro), rs761630889, gnomAD 12-12717917-C-A, CADD 12.20
- S27* (p.Ser27Ter), NCI-TCGA Cosmic COSV5743, cosmic curated COSV57431, NCI-TCGA Cosmic COSV9996, Variant assessed as somatic; high impact.
- S27L (p.Ser27Leu), rs1060500190, ClinGen CA16613529, cosmic curated COSV99963, ClinVar RCV000472255, REVEL 0.52, CADD 29.20, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- S27P (p.Ser27Pro), rs1946487784, ClinGen CA383968389, ClinVar RCV003301872, Ensembl rs1946487784, AlphaMissense 0.20, MetaLR 0.73, Uncertain significance, Hereditary cancer-predisposing syndrome
- S27T (p.Ser27Thr), Ensembl rs1946487784, Uncertain significance
- S27S (p.Ser27Ser), rs1367446982, gnomAD 12-12717920-G-A, CADD 12.20
- A28D (p.Ala28Asp), rs1592280774, ClinGen CA383968398, ClinVar RCV002434896, ClinVar RCV003099931, AlphaMissense 0.51, MetaLR 0.50, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- A28S (p.Ala28Ser), rs2497403970, ClinGen CA383968395, ClinVar RCV004516454, Uncertain significance, Hereditary cancer-predisposing syndrome
- A28V (p.Ala28Val), rs1592280774, ClinGen CA383968407, ClinVar RCV001210314, ClinVar RCV001773471, REVEL 0.58, AlphaMissense 0.51, Uncertain significance, not provided; Hereditary cancer-predisposing syndrome; Multiple endocrine neopla
- C29F (p.Cys29Phe), NCI-TCGA Cosmic COSV9996, cosmic curated COSV99963, Variant assessed as somatic; moderate impact.
- C29R (p.Cys29Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- C29Y (p.Cys29Tyr), rs1946487948, ClinGen CA383968429, cosmic curated COSV10584, ClinVar RCV001207546, REVEL 0.87, CADD 31.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- C29C (p.Cys29Cys), rs767234696, gnomAD 12-12717926-C-T, CADD 14.80
- R30S (p.Arg30Ser), NCI-TCGA TCGA novel, REVEL 0.78, CADD 22.70, Variant assessed as somatic; high impact.
- N31H (p.Asn31His), rs2497404007, ClinGen CA383968480, ClinVar RCV003509443, Uncertain significance, Multiple endocrine neoplasia type 4
- N31K (p.Asn31Lys), rs577554685, ClinGen CA383968505, ClinVar RCV001914807, ClinVar RCV005792189, REVEL 0.56, CADD 25.30, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- N31Y (p.Asn31Tyr), rs2497404007, ClinGen CA383968487, ClinVar RCV003015901, Uncertain significance, Multiple endocrine neoplasia type 4
- N31I (p.Asn31Ile), gnomAD 12-12717931-A-T, REVEL 0.63, CADD 26.50
- N31N (p.Asn31Asn), rs577554685, gnomAD 12-12717932-C-T, CADD 13.30
- L32F (p.Leu32Phe), rs2136355531, ClinGen CA383968517, cosmic curated COSV57430, ClinVar RCV001910531, AlphaMissense 0.99, MetaLR 0.84, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- L32I (p.Leu32Ile), gnomAD 12-12717933-C-A, REVEL 0.75, CADD 23.90
- L32L (p.Leu32Leu), rs1202654522, gnomAD 12-12717935-C-T, CADD 13.10
- F33L (p.Phe33Leu), rs201349921, ClinGen CA383968569, ClinVar RCV001211729, ClinVar RCV002379802, AlphaMissense 1.00, MetaLR 0.80, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Multiple endocrine neopla
- F33F (p.Phe33Phe), rs201349921, gnomAD 12-12717938-C-T, AlphaMissense 1.00, MetaLR 0.80
- G34D (p.Gly34Asp), Ensembl rs2136355545
- G34R (p.Gly34Arg), Ensembl rs1946488422, Uncertain significance
- G34S (p.Gly34Ser), rs1946488422, ClinGen CA383968577, ClinVar RCV001067938, Ensembl rs1946488422, AlphaMissense 1.00, MetaLR 0.82, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- G34G (p.Gly34Gly), rs2136355548, gnomAD 12-12717941-C-T, CADD 12.80
- P35A (p.Pro35Ala), rs1946488503, ClinGen CA383968611, ClinVar RCV001327314, Ensembl rs1946488503, AlphaMissense 0.19, MetaLR 0.75, Uncertain significance, Multiple endocrine neoplasia type 4
- P35L (p.Pro35Leu), rs375297371, ClinGen CA6457378, cosmic curated COSV57431, NCI-TCGA Cosmic COSV9996, REVEL 0.72, AlphaMissense 0.42, Uncertain significance, Hereditary cancer-predisposing syndrome; not provided; Multiple endocrine neopla
- P35Q (p.Pro35Gln), ESP rs375297371, ExAC rs375297371, TOPMed rs375297371, gnomAD rs375297371, Uncertain significance
- P35R (p.Pro35Arg), rs375297371, ClinGen CA383968625, ClinVar RCV002401043, AlphaMissense 0.42, MetaLR 0.89, Uncertain significance, Hereditary cancer-predisposing syndrome
- P35S (p.Pro35Ser), rs1946488503, ClinGen CA383968615, ClinVar RCV003511102, AlphaMissense 0.19, MetaLR 0.75, Uncertain significance, Multiple endocrine neoplasia type 4
- P35P (p.Pro35Pro), rs1207298217, gnomAD 12-12717944-G-C, CADD 11.30
- V36G (p.Val36Gly), rs2497404080, ClinGen CA383968654, ClinVar RCV002417538, ClinVar RCV003098629, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- V36L (p.Val36Leu), ExAC rs753931778, gnomAD rs753931778, REVEL 0.63, CADD 25.00
- V36M (p.Val36Met), ExAC rs753931778, gnomAD rs753931778, REVEL 0.70, CADD 29.70
- D37E (p.Asp37Glu), rs1565419320, ClinGen CA383968684, ClinVar RCV000690919, ClinVar RCV002255507, AlphaMissense 0.69, MetaLR 0.69, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- D37G (p.Asp37Gly), rs2497404091, ClinGen CA383968675, ClinVar RCV002847740, ClinVar RCV003167843, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- D37N (p.Asp37Asn), rs1946488666, ClinGen CA383968660, cosmic curated COSV57431, ClinVar RCV001312928, AlphaMissense 0.07, MetaLR 0.57, Uncertain significance, Multiple endocrine neoplasia type 4
- H38L (p.His38Leu), Ensembl rs2136355571
- H38Q (p.His38Gln), 1000Genomes rs141178987, ESP rs141178987, ExAC rs141178987, TOPMed rs141178987, Benign
- H38Y (p.His38Tyr), rs1592280791, ClinGen CA383968696, ClinVar RCV000804681, Ensembl rs1592280791, AlphaMissense 0.83, MetaLR 0.79, Uncertain significance, Multiple endocrine neoplasia type 4
- H38H (p.His38His), rs141178987, gnomAD 12-12717953-C-T, CADD 12.60
- E39* (p.Glu39Ter), rs1592280796, ClinGen CA383968716, ClinVar RCV003619275, NCI-TCGA Cosmic COSV5743, AlphaMissense 0.10, MetaLR 0.67, Pathogenic
- E39G (p.Glu39Gly), TOPMed rs1239628688, gnomAD rs1239628688, REVEL 0.64, CADD 31.00, Uncertain significance, Hereditary cancer-predisposing syndrome
- E39K (p.Glu39Lys), rs1592280796, ClinGen CA383968713, cosmic curated COSV10955, ClinVar RCV000802743, REVEL 0.67, AlphaMissense 0.10, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- E39Q (p.Glu39Gln), rs1592280796, ClinGen CA383968720, NCI-TCGA Cosmic COSV5743, NCI-TCGA Cosmic COSV9996, AlphaMissense 0.10, MetaLR 0.67, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- E40K (p.Glu40Lys), rs765527234, ClinGen CA6457382, cosmic curated COSV57431, ClinVar RCV002254867, REVEL 0.71, CADD 26.40, Conflicting interpretations, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- E40E (p.Glu40Glu), rs752899815, gnomAD 12-12717959-G-A, CADD 12.60
- L41* (p.Leu41Ter), NCI-TCGA Cosmic COSV9996, cosmic curated COSV99964, Variant assessed as somatic; high impact.
- L41L (p.Leu41Leu), rs758843248, gnomAD 12-12717960-T-C, CADD 12.80
- T42A (p.Thr42Ala), rs1592280811, ClinGen CA383968780, cosmic curated COSV57431, ClinVar RCV000807037, REVEL 0.19, CADD 22.30, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- T42I (p.Thr42Ile), rs200422211, ClinGen CA6457385, cosmic curated COSV57430, ClinVar RCV000463157, REVEL 0.26, AlphaMissense 0.34, Conflicting interpretations, Hereditary cancer-predisposing syndrome; not provided; Multiple endocrine neopla
- T42S (p.Thr42Ser), rs200422211, ClinGen CA383968793, ClinVar RCV001339029, ClinVar RCV002431945, AlphaMissense 0.34, MetaLR 0.42, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- T42L (p.Thr42Leu), gnomAD 12-12717961-TAACC, CADD 33.00
- T42T (p.Thr42Thr), rs747582957, gnomAD 12-12717965-C-T, CADD 13.00
- R43* (p.Arg43Ter), rs797044481, ClinGen CA212533, ClinVar RCV000191951, Ensembl rs797044481, Likely pathogenic
- R43L (p.Arg43Leu), cosmic curated COSV10955, gnomAD rs1174071842, REVEL 0.61, CADD 32.00
- R43W (p.Arg43Trp), rs1946489200, ClinGen CA383968799, ClinVar RCV003619858, gnomAD rs1946489200, REVEL 0.57, CADD 27.40, Uncertain significance, Multiple endocrine neoplasia type 4
- R43Q (p.Arg43Gln), gnomAD 12-12717967-G-A, REVEL 0.37, CADD 26.10
- R43R (p.Arg43Arg), rs757748971, gnomAD 12-12717968-G-C, CADD 13.40
- D44G (p.Asp44Gly), rs748854742, ClinGen CA6457389, cosmic curated COSV10456, ClinVar RCV000473902, REVEL 0.73, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- D44H (p.Asp44His), rs2136355606, ClinGen CA383968845, ClinVar RCV002002132, ClinVar RCV004946909, REVEL 0.73, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- D44N (p.Asp44Asn), rs2136355606, ClinGen CA383968839, NCI-TCGA Cosmic COSV5742, cosmic curated COSV57429, REVEL 0.60, CADD 32.00, Uncertain significance, Hereditary cancer-predisposing syndrome; Multiple endocrine neoplasia type 4
- D44Y (p.Asp44Tyr), rs2136355606, ClinGen CA383968849, ClinVar RCV002031432, ClinVar RCV005308699, REVEL 0.70, CADD 32.00, Uncertain significance, Multiple endocrine neoplasia type 4; Hereditary cancer-predisposing syndrome
- D44D (p.Asp44Asp), rs1946489417, gnomAD 12-12717971-C-T, CADD 13.80
- L45V (p.Leu45Val), rs2497404236, ClinGen CA383968879, ClinVar RCV004516434, Uncertain significance, Hereditary cancer-predisposing syndrome
- L45W (p.Leu45Trp), rs2136355613, ClinGen CA383968882, ClinVar RCV001992736, Ensembl rs2136355613, REVEL 0.62, CADD 32.00, Uncertain significance, Multiple endocrine neoplasia type 4
- L45L (p.Leu45Leu), rs2136355617, gnomAD 12-12717974-G-A, CADD 13.90
- L45F (p.Leu45Phe), gnomAD 12-12717974-G-C, REVEL 0.39, MetaLR 0.31
- E46G (p.Glu46Gly), rs1592280829, ClinGen CA383968901, cosmic curated COSV57430, ClinVar RCV001011258, AlphaMissense 0.18, MetaLR 0.38, Uncertain significance, Hereditary cancer-predisposing syndrome
- E46Q (p.Glu46Gln), rs2497404246, ClinGen CA383968891, ClinVar RCV002839576, Uncertain significance, Multiple endocrine neoplasia type 4
- E46K (p.Glu46Lys), gnomAD 12-12717975-G-A, REVEL 0.20, MetaLR 0.15
- E46E (p.Glu46Glu), rs2136355621, gnomAD 12-12717977-G-A, CADD 13.30
- K47N (p.Lys47Asn), rs2136355630, ClinGen CA383968922, ClinVar RCV003042614, Uncertain significance, Multiple endocrine neoplasia type 4
Public CDKN1B analysis runs
- CDKN1B analysis run — CDKN1B (924 variants) — completed 2026-08-21