IL12RB1 (P42701) variants and mutations
IL12RB1 (also known as P42701) is a human protein-coding gene encoding an interleukin-12 receptor subunit beta-1 protein. It is shared by IL-12 and IL-23 receptor complexes and is required for effective Th1 and Th17 immune responses. Biallelic loss-of-function variants are a common genetic cause of Mendelian susceptibility to mycobacterial disease. This analysis covers 1,181 IL12RB1 variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes immunodeficiency disease, Oral ulcer, and systemic sclerosis. Example IL12RB1 variants include E2G, P3L, and P3Q.
Variant analysis overview
- Gene: IL12RB1
- Protein: P42701
- UniProt accession: P42701
- Organism: Homo sapiens
- Variants analyzed: 1181
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 948 unspecified-consequence records; 132 missense variants; 4 splice-region variants; 66 synonymous variants; 14 frameshift variants; 14 stop-gained variants; 2 in-frame deletions; 2 substitution
- Prediction scores: 895 variants have prediction scores (76% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: immunodeficiency disease, Oral ulcer, systemic sclerosis, hereditary disease, immune system disorder, brain cancer, nervous system cancer, Familial exudative vitreoretinopathy, retinitis pigmentosa, Leber congenital amaurosis, posterior polymorphous corneal dystrophy, tuberculosis.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 5 domains; 6 post-translational modification sites.
- Structural context: 747 variants have structural context.
- PTM context: 10 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable IL12RB1 variants
Examples include E2G, P3L, P3Q, P3R, V5G, V5L, V5M, T6P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2G (p.Glu2Gly), Ensembl rs2146505929, CADD 7.63, PolyPhen-2 0.00
- P3L (p.Pro3Leu), rs17884651, ClinGen CA9305398, ClinVar RCV001124438, 1000Genomes rs17884651, CADD 5.34, PolyPhen-2 0.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- P3Q (p.Pro3Gln), rs17884651, ClinGen CA306141563, ClinVar RCV001987757, UniProt VAR 021281, CADD 4.14, PolyPhen-2 0.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- P3R (p.Pro3Arg), NCI-TCGA TCGA novel, CADD 4.24, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- V5G (p.Val5Gly), Ensembl rs1599579136
- V5L (p.Val5Leu), gnomAD rs1568526239, CADD 16.10, PolyPhen-2 0.00
- V5M (p.Val5Met), gnomAD rs1568526239
- T6P (p.Thr6Pro), Ensembl rs2146505493
- W7* (p.Trp7Ter), TOPMed rs150172855, CADD 34.00
- W7R (p.Trp7Arg), rs775656716, ClinGen CA404791388, cosmic curated COSV59096, ClinVar RCV001320526, CADD 4.36, PolyPhen-2 0.00, Likely benign, Inborn genetic diseases
- V9A (p.Val9Ala), cosmic curated COSV59097
- P10H (p.Pro10His), rs745474746, ClinGen CA9305395, ClinVar RCV000802361, ClinVar RCV004986612, CADD 15.00, PolyPhen-2 0.43, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- P10L (p.Pro10Leu), cosmic curated COSV59098
- P10S (p.Pro10Ser), cosmic curated COSV59098, CADD 11.60, PolyPhen-2 0.04
- L11F (p.Leu11Phe), gnomAD rs1178944190, CADD 5.78, PolyPhen-2 0.31
- L12I (p.Leu12Ile), cosmic curated COSV10044
- F13L (p.Phe13Leu), cosmic curated COSV10737
- L14I (p.Leu14Ile), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10044, Variant assessed as somatic; moderate impact.
- F15L (p.Phe15Leu), gnomAD rs1429095330, CADD 1.46, PolyPhen-2 0.00, Uncertain significance
- F15V (p.Phe15Val), rs1429095330, ClinGen CA404791244, ClinVar RCV001207387, gnomAD rs1429095330, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- F15Y (p.Phe15Tyr), Ensembl rs1599578894
- L17P (p.Leu17Pro), ExAC rs770755723, gnomAD rs770755723, CADD 10.20, PolyPhen-2 0.12
- S18F (p.Ser18Phe), cosmic curated COSV59097, CADD 1.68, PolyPhen-2 0.11
- R19G (p.Arg19Gly), rs746501773, ClinGen CA9305392, ClinVar RCV002008364, ExAC rs746501773, CADD 8.58, PolyPhen-2 0.01, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- R19K (p.Arg19Lys), TOPMed rs1310287396, gnomAD rs1310287396, CADD 3.03, PolyPhen-2 0.01
- Q20H (p.Gln20His), cosmic curated COSV10044
- Q20K (p.Gln20Lys), cosmic curated COSV59097
- G21D (p.Gly21Asp), Ensembl rs2036370556, CADD 15.20, PolyPhen-2 0.15
- G21S (p.Gly21Ser), rs758204377, ClinGen CA9305390, ClinVar RCV001964901, ClinVar RCV004041856, CADD 2.07, PolyPhen-2 0.00, Uncertain significance, Inborn genetic diseases; Mendelian susceptibility to mycobacterial diseases due
- A22T (p.Ala22Thr), ExAC rs778524238, gnomAD rs778524238, CADD 25.00, PolyPhen-2 0.05
- A23V (p.Ala23Val), gnomAD rs1244613582
- R25K (p.Arg25Lys), 1000Genomes rs200783433, ExAC rs200783433, gnomAD rs200783433, CADD 7.07, PolyPhen-2 0.01
- E28A (p.Glu28Ala), ExAC rs757407762, TOPMed rs757407762, gnomAD rs757407762, CADD 6.32, PolyPhen-2 0.01, Likely benign
- E28G (p.Glu28Gly), rs757407762, ClinGen CA404790570, ClinVar RCV002903533, ClinVar RCV002903534, CADD 7.96, PolyPhen-2 0.00, Conflicting interpretations, Inborn genetic diseases; Mendelian susceptibility to mycobacterial diseases due
- E28K (p.Glu28Lys), ExAC rs779895710, gnomAD rs779895710, CADD 8.81, PolyPhen-2 0.03
- C29* (p.Cys29Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- F31L (p.Phe31Leu), cosmic curated COSV59099
- Q32* (p.Gln32Ter), rs121434492, ClinGen CA119239, ClinVar RCV000008497, ClinVar RCV000725837, CADD 38.00, Pathogenic
- D33A (p.Asp33Ala), ExAC rs777672951, gnomAD rs777672951, CADD 22.20, PolyPhen-2 0.40
- D33H (p.Asp33His), gnomAD rs1368017385, CADD 22.70, PolyPhen-2 0.75
- D33Y (p.Asp33Tyr), NCI-TCGA Cosmic COSV5909, cosmic curated COSV59096, Variant assessed as somatic; moderate impact.
- P34L (p.Pro34Leu), rs113524129, ClinGen CA9305362, cosmic curated COSV59096, ClinVar RCV001124437, CADD 0.04, PolyPhen-2 0.07, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- P34S (p.Pro34Ser), ExAC rs202206502, TOPMed rs202206502, gnomAD rs202206502, CADD 15.40, PolyPhen-2 0.37
- P34T (p.Pro34Thr), cosmic curated COSV59097
- Y36H (p.Tyr36His), ExAC rs760186873, gnomAD rs760186873, CADD 22.20, PolyPhen-2 0.88
- P37L (p.Pro37Leu), rs142484991, ClinGen CA9305358, cosmic curated COSV59097, ClinVar RCV001047753, CADD 15.00, PolyPhen-2 0.67, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- P37Q (p.Pro37Gln), cosmic curated COSV59096
- P37T (p.Pro37Thr), rs754187694, ClinGen CA9305359, ClinVar RCV001893048, ExAC rs754187694, CADD 4.31, PolyPhen-2 0.37, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- D38A (p.Asp38Ala), gnomAD rs1266683292, CADD 17.80, PolyPhen-2 0.02
- D40N (p.Asp40Asn), cosmic curated COSV59096
- D40Y (p.Asp40Tyr), NCI-TCGA Cosmic COSV5909, Variant assessed as somatic; moderate impact.
- S41P (p.Ser41Pro), rs772951042, ClinGen CA9305355, ClinVar RCV002952220, ExAC rs772951042, CADD 8.27, PolyPhen-2 0.00, Uncertain significance, Inborn genetic diseases
- G42D (p.Gly42Asp), ExAC rs745661790, gnomAD rs745661790, CADD 21.40, PolyPhen-2 1.00
- S43L (p.Ser43Leu), rs189309495, ClinGen CA9305329, ClinVar RCV001932205, ClinVar RCV003987918, CADD 16.00, PolyPhen-2 0.03, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- A44T (p.Ala44Thr), TOPMed rs2035969537, gnomAD rs2035969537, CADD 2.12, PolyPhen-2 0.11
- A44V (p.Ala44Val), rs372265041, ClinGen CA9305326, ClinVar RCV000813814, ESP rs372265041, CADD 14.70, PolyPhen-2 0.55, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- S45* (p.Ser45Ter), cosmic curated COSV10737
- S45L (p.Ser45Leu), rs150070244, ClinGen CA9305325, ClinVar RCV000818940, ESP rs150070244, CADD 3.87, PolyPhen-2 0.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- G46D (p.Gly46Asp), ExAC rs749421416, TOPMed rs749421416, gnomAD rs749421416, CADD 23.40, PolyPhen-2 1.00, Uncertain significance, Inborn genetic diseases
- G46S (p.Gly46Ser), cosmic curated COSV10522, TOPMed rs1418391865
- P47H (p.Pro47His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P47R (p.Pro47Arg), ExAC rs756640017, gnomAD rs756640017, CADD 24.00, PolyPhen-2 1.00
- P47S (p.Pro47Ser), rs17887176, ClinGen CA9305321, ClinVar RCV000548053, ClinVar RCV004717231, CADD 24.00, PolyPhen-2 1.00, Benign, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- R48G (p.Arg48Gly), rs1568517733, ClinGen CA404790371, ClinVar RCV000690616, Ensembl rs1568517733, CADD 21.10, PolyPhen-2 0.95, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- R48K (p.Arg48Lys), rs750798813, ClinGen CA9305319, ClinVar RCV001123350, ExAC rs750798813, CADD 9.79, PolyPhen-2 0.90, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- R48W (p.Arg48Trp), cosmic curated COSV10044
- D49E (p.Asp49Glu), TOPMed rs2035966738, CADD 17.50, PolyPhen-2 0.20
- D49N (p.Asp49Asn), ExAC rs767782063, TOPMed rs767782063, gnomAD rs767782063, CADD 0.01, PolyPhen-2 0.01
- L50P (p.Leu50Pro), cosmic curated COSV10044, CADD 21.60, PolyPhen-2 0.06
- L50R (p.Leu50Arg), cosmic curated COSV10881, CADD 23.30, PolyPhen-2 0.91
- R51T (p.Arg51Thr), ESP rs150816599, ExAC rs150816599, gnomAD rs150816599, CADD 7.40, PolyPhen-2 0.01
- C52* (p.Cys52Ter), cosmic curated COSV59098
- Y53C (p.Tyr53Cys), rs1300166633, ClinGen CA404790305, ClinVar RCV002792121, TOPMed rs1300166633, CADD 25.70, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- R54G (p.Arg54Gly), ESP rs367796048, ExAC rs367796048, TOPMed rs367796048, gnomAD rs367796048, CADD 25.20, PolyPhen-2 0.99, Uncertain significance
- R54Q (p.Arg54Gln), rs377441024, ClinGen CA9305314, ClinVar RCV001123349, 1000Genomes rs377441024, CADD 26.50, PolyPhen-2 0.82, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- R54W (p.Arg54Trp), rs367796048, ClinGen CA9305315, ClinVar RCV001206881, ESP rs367796048, CADD 26.00, PolyPhen-2 1.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- I55L (p.Ile55Leu), gnomAD rs1222616575, CADD 13.20, PolyPhen-2 0.00
- I55M (p.Ile55Met), TOPMed rs1276919423, gnomAD rs1276919423, CADD 8.90, PolyPhen-2 0.12
- S56F (p.Ser56Phe), cosmic curated COSV59096, Ensembl rs990803121, CADD 3.46, PolyPhen-2 0.00
- S57G (p.Ser57Gly), gnomAD rs1350010302, CADD 2.21, PolyPhen-2 0.00
- R59C (p.Arg59Cys), rs865858530, NCI-TCGA Cosmic COSV5909, cosmic curated COSV59096, TOPMed rs865858530, CADD 7.52, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- R59H (p.Arg59His), rs142273743, ClinGen CA9305313, NCI-TCGA Cosmic COSV5909, cosmic curated COSV59097, CADD 0.56, PolyPhen-2 0.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- R59S (p.Arg59Ser), rs865858530, NCI-TCGA Cosmic COSV5909, TOPMed rs865858530, gnomAD rs865858530, CADD 1.73, PolyPhen-2 0.00, Variant assessed as somatic; moderate impact.
- Y60C (p.Tyr60Cys), ESP rs140770932, ExAC rs140770932, TOPMed rs140770932, gnomAD rs140770932, CADD 23.30, PolyPhen-2 0.82
- E61* (p.Glu61Ter), cosmic curated COSV10044, 1000Genomes rs117720235, ExAC rs117720235, TOPMed rs117720235, CADD 36.00, Uncertain significance
- E61D (p.Glu61Asp), ExAC rs770654289, TOPMed rs770654289, gnomAD rs770654289
- E61K (p.Glu61Lys), rs117720235, ClinGen CA9305310, ClinVar RCV000808544, 1000Genomes rs117720235, CADD 20.90, PolyPhen-2 0.30, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- S63F (p.Ser63Phe), cosmic curated COSV10522, Ensembl rs1487019991
- W64C (p.Trp64Cys), rs2035963299, ClinGen CA404790145, ClinVar RCV001343325, Ensembl rs2035963299, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- Q65* (p.Gln65Ter), gnomAD rs1301185388, CADD 36.00
- Y66H (p.Tyr66His), gnomAD rs1403702969, CADD 23.80
- E67K (p.Glu67Lys), ExAC rs748341357, TOPMed rs748341357, gnomAD rs748341357, CADD 18.60, PolyPhen-2 0.13
- G68C (p.Gly68Cys), rs538026254, ClinGen CA9305306, ClinVar RCV002807346, 1000Genomes rs538026254, CADD 29.80, PolyPhen-2 1.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- G68V (p.Gly68Val), rs749368055, ClinGen CA9305305, ClinVar RCV002613602, ExAC rs749368055, CADD 24.20, PolyPhen-2 1.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- P69L (p.Pro69Leu), rs756580080, ClinGen CA9305303, cosmic curated COSV10464, ClinVar RCV002807040, CADD 24.10, PolyPhen-2 0.99, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- P69S (p.Pro69Ser), ESP rs373626971, ExAC rs373626971, TOPMed rs373626971, gnomAD rs373626971, CADD 13.50, PolyPhen-2 0.76
- T70I (p.Thr70Ile), rs950913087, ClinGen CA306137442, ClinVar RCV001236981, TOPMed rs950913087, CADD 8.52, PolyPhen-2 0.20, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- G72E (p.Gly72Glu), ExAC rs746380216
- V73A (p.Val73Ala), gnomAD rs1214227502
- S74N (p.Ser74Asn), NCI-TCGA Cosmic COSV5909, cosmic curated COSV59098, Ensembl rs2146414715, CADD 13.60, PolyPhen-2 0.01, Variant assessed as somatic; moderate impact.
- S74R (p.Ser74Arg), rs11575925, ClinGen CA9305301, cosmic curated COSV10522, ClinVar RCV000487869, CADD 21.10, PolyPhen-2 0.46, Likely benign, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- H75L (p.His75Leu), TOPMed rs2035960973
- F76V (p.Phe76Val), NCI-TCGA Cosmic COSV1004, cosmic curated COSV10044, Variant assessed as somatic; moderate impact.
- L77P (p.Leu77Pro), TOPMed rs1412769589, gnomAD rs1412769589, CADD 25.10, PolyPhen-2 1.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- L77R (p.Leu77Arg), TOPMed rs1412769589, gnomAD rs1412769589, CADD 24.30
- R78Q (p.Arg78Gln), rs1357460137, TOPMed rs1357460137, gnomAD rs1357460137, CADD 11.60, PolyPhen-2 0.27, Variant assessed as somatic; moderate impact.
- R78W (p.Arg78Trp), rs751966500, ClinGen CA9305299, ClinVar RCV001364210, ExAC rs751966500, CADD 6.14, PolyPhen-2 0.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- C79R (p.Cys79Arg), ExAC rs777387135, gnomAD rs777387135, CADD 15.90, PolyPhen-2 0.38
- C79Y (p.Cys79Tyr), ESP rs370818889, ExAC rs370818889, TOPMed rs370818889, gnomAD rs370818889, CADD 20.40, PolyPhen-2 0.02
- L81F (p.Leu81Phe), Ensembl rs2035861136
- S83Y (p.Ser83Tyr), gnomAD rs1477691936, CADD 2.93, PolyPhen-2 0.03
- G84A (p.Gly84Ala), rs1568515222, ClinGen CA891843883, ClinVar RCV000704573, Pathogenic
- G84E (p.Gly84Glu), gnomAD rs1479760533, CADD 7.17, PolyPhen-2 0.04
- G84R (p.Gly84Arg), rs757986795, NCI-TCGA TCGA novel, ClinGen CA9305278, ClinVar RCV001231529, CADD 6.71, PolyPhen-2 0.19, Uncertain significance, Inborn genetic diseases; Mendelian susceptibility to mycobacterial diseases due
- R85C (p.Arg85Cys), rs138859377, ClinGen CA9305277, ClinVar RCV003092129, ESP rs138859377, CADD 12.90, PolyPhen-2 0.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- R85H (p.Arg85His), rs754415781, ClinGen CA9305275, ClinVar RCV001980395, ClinVar RCV004989037, CADD 4.06, PolyPhen-2 0.29, Uncertain significance, Inborn genetic diseases; Mendelian susceptibility to mycobacterial diseases due
- R85L (p.Arg85Leu), ExAC rs754415781, TOPMed rs754415781, gnomAD rs754415781, CADD 4.30, PolyPhen-2 0.05, Uncertain significance
- C86W (p.Cys86Trp), Ensembl rs2035859733, CADD 22.50, PolyPhen-2 0.91
- C86Y (p.Cys86Tyr), ExAC rs753438288, gnomAD rs753438288, CADD 24.00, PolyPhen-2 0.82
- Y88* (p.Tyr88Ter), rs1202592147, ClinGen CA404789960, ClinVar RCV000788565, ClinVar RCV004027370, Pathogenic
- Y88H (p.Tyr88His), gnomAD rs1198312612, CADD 21.50, PolyPhen-2 0.46
- F89L (p.Phe89Leu), ExAC rs375546243, TOPMed rs375546243, gnomAD rs375546243, CADD 0.41, PolyPhen-2 0.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- A90D (p.Ala90Asp), cosmic curated COSV59098, TOPMed rs1344824078, gnomAD rs1344824078, CADD 3.64, PolyPhen-2 0.14
- A90T (p.Ala90Thr), rs144128347, ClinGen CA9305270, ClinVar RCV001209446, ESP rs144128347, CADD 0.00, PolyPhen-2 0.04, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- A91S (p.Ala91Ser), 1000Genomes rs147215816, ExAC rs147215816, TOPMed rs147215816, gnomAD rs147215816, CADD 0.40, PolyPhen-2 0.01, Benign
- A91T (p.Ala91Thr), rs147215816, ClinGen CA9305267, cosmic curated COSV10737, ClinVar RCV000652151, CADD 0.79, PolyPhen-2 0.00, Benign, not provided; Mendelian susceptibility to mycobacterial diseases due to complete
- G92C (p.Gly92Cys), cosmic curated COSV99078
- G92S (p.Gly92Ser), rs776835424, ClinGen CA9305265, ClinVar RCV001248394, ExAC rs776835424, CADD 22.80, PolyPhen-2 0.87, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- A94D (p.Ala94Asp), cosmic curated COSV10589, CADD 10.70, PolyPhen-2 0.00
- A94T (p.Ala94Thr), rs747526703, ClinGen CA9305263, ClinVar RCV001213078, ExAC rs747526703, CADD 9.92, PolyPhen-2 0.04, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- T95I (p.Thr95Ile), rs778062013, ClinGen CA9305262, ClinVar RCV001331413, ClinVar RCV004987084, CADD 20.60, PolyPhen-2 0.30, Uncertain significance, Inborn genetic diseases; Mendelian susceptibility to mycobacterial diseases due
- R96G (p.Arg96Gly), gnomAD rs2035857373, CADD 5.37
- Q98R (p.Gln98Arg), gnomAD rs1377559024, CADD 3.24, PolyPhen-2 0.10
- F99I (p.Phe99Ile), gnomAD rs1183245601, CADD 22.60, PolyPhen-2 0.04
- D101H (p.Asp101His), ExAC rs748586854, TOPMed rs748586854, gnomAD rs748586854, CADD 23.90, PolyPhen-2 0.89, Uncertain significance
- D101N (p.Asp101Asn), rs748586854, ClinGen CA404789888, cosmic curated COSV10589, ClinVar RCV001362146, CADD 23.60, PolyPhen-2 0.49, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- D101V (p.Asp101Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q102* (p.Gln102Ter), rs2035855899, ClinGen CA404789879, ClinVar RCV003022741, Pathogenic
- Q102K (p.Gln102Lys), rs2035855899, ClinGen CA404789881, ClinVar RCV003749528, TOPMed rs2035855899, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- A103D (p.Ala103Asp), cosmic curated COSV59098
- A103P (p.Ala103Pro), ExAC rs778409675, CADD 20.50, PolyPhen-2 0.19
- G104E (p.Gly104Glu), rs1568514893, NCI-TCGA Cosmic COSV5909, cosmic curated COSV59096, gnomAD rs1568514893, CADD 9.69, PolyPhen-2 0.05, Variant assessed as somatic; moderate impact.
- G104R (p.Gly104Arg), Ensembl rs1568514904
- G104W (p.Gly104Trp), cosmic curated COSV10044
- V105G (p.Val105Gly), Ensembl rs1599548212
- V105L (p.Val105Leu), rs756061336, ClinGen CA404789861, ClinVar RCV002777785, ExAC rs756061336, CADD 5.12, PolyPhen-2 0.06, Uncertain significance, Inborn genetic diseases
- V105M (p.Val105Met), ExAC rs756061336, TOPMed rs756061336, gnomAD rs756061336, Uncertain significance
- V107A (p.Val107Ala), rs150285174, ClinGen CA9305253, cosmic curated COSV59097, ClinVar RCV000931149, CADD 17.50, PolyPhen-2 0.06, Conflicting interpretations, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- Y109S (p.Tyr109Ser), cosmic curated COSV10737
- T110A (p.Thr110Ala), ExAC rs751425121, gnomAD rs751425121, CADD 0.04, PolyPhen-2 0.00
- T110I (p.Thr110Ile), ExAC rs765371000, TOPMed rs765371000, gnomAD rs765371000, CADD 0.01, PolyPhen-2 0.03, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- V111I (p.Val111Ile), rs1175476350, NCI-TCGA Cosmic COSV1004, cosmic curated COSV10044, gnomAD rs1175476350, CADD 14.50, PolyPhen-2 0.02, Variant assessed as somatic; moderate impact.
- T112I (p.Thr112Ile), gnomAD rs1452847398, CADD 15.50, PolyPhen-2 0.04
- L113R (p.Leu113Arg), TOPMed rs2035853301
- W114* (p.Trp114Ter), ESP rs372512479, ExAC rs372512479, TOPMed rs372512479, gnomAD rs372512479, CADD 37.00
- W114S (p.Trp114Ser), ESP rs372512479, ExAC rs372512479, TOPMed rs372512479, gnomAD rs372512479, CADD 24.30, PolyPhen-2 0.58, Uncertain significance, Inborn genetic diseases
- A119P (p.Ala119Pro), ExAC rs761129935, gnomAD rs761129935, CADD 10.40, PolyPhen-2 0.28
- A119S (p.Ala119Ser), cosmic curated COSV59099
- R120S (p.Arg120Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R120T (p.Arg120Thr), rs1455838206, ClinGen CA404789767, ClinVar RCV004404939, gnomAD rs1455838206, CADD 0.01, PolyPhen-2 0.01, Uncertain significance, Inborn genetic diseases
- R120W (p.Arg120Trp), gnomAD rs1159627144, CADD 14.20, PolyPhen-2 0.32
- N121K (p.Asn121Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N121S (p.Asn121Ser), cosmic curated COSV10605
- Q122H (p.Gln122His), cosmic curated COSV10044
- T123A (p.Thr123Ala), Ensembl rs878915625, CADD 12.00, PolyPhen-2 0.05
- T123I (p.Thr123Ile), TOPMed rs531901903, gnomAD rs531901903, CADD 14.70, PolyPhen-2 0.07
- T123R (p.Thr123Arg), TOPMed rs531901903, gnomAD rs531901903
- E124K (p.Glu124Lys), rs772617080, ClinGen CA9305243, ClinVar RCV001221641, ExAC rs772617080, CADD 7.67, PolyPhen-2 0.03, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- E124Q (p.Glu124Gln), rs772617080, ClinGen CA404789743, ClinVar RCV001979291, ExAC rs772617080, CADD 4.61, PolyPhen-2 0.00, Uncertain significance, Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 defic
- E124R (p.Glu124Arg), rs2146389344, ClinGen CA2573054740, ClinVar RCV001779409, Pathogenic
- S126F (p.Ser126Phe), NCI-TCGA Cosmic COSV5909, cosmic curated COSV59098, Variant assessed as somatic; moderate impact.
- P127A (p.Pro127Ala), cosmic curated COSV10815, CADD 0.69, PolyPhen-2 0.01
- P127L (p.Pro127Leu), ExAC rs774846440, TOPMed rs774846440, gnomAD rs774846440, CADD 11.20, PolyPhen-2 0.01, Uncertain significance, Inborn genetic diseases
- P127R (p.Pro127Arg), ExAC rs774846440, TOPMed rs774846440, gnomAD rs774846440, CADD 14.90, PolyPhen-2 0.08, Uncertain significance
- P127S (p.Pro127Ser), TOPMed rs984925737
- E128Q (p.Glu128Gln), cosmic curated COSV59099
- T130N (p.Thr130Asn), TOPMed rs1189853035, gnomAD rs1189853035, CADD 7.63, PolyPhen-2 0.08
- T130S (p.Thr130Ser), TOPMed rs1189853035, gnomAD rs1189853035, CADD 10.40, PolyPhen-2 0.01
- Q132* (p.Gln132Ter), rs1284613041, ClinGen CA404789695, cosmic curated COSV10044, ClinVar RCV003146200, CADD 35.00, Likely pathogenic
- Q132H (p.Gln132His), gnomAD rs1724438341, CADD 0.06, PolyPhen-2 0.10, Uncertain significance, Inborn genetic diseases
Public IL12RB1 analysis runs
- IL12RB1 analysis run — IL12RB1 (1,181 variants) — completed 2026-08-22