TYK2 (P29597) variants and mutations
TYK2 (also known as P29597) is a human protein-coding gene encoding a non-receptor tyrosine-protein kinase protein. It transmits signals from type I interferon, IL-12, IL-23, and related cytokine receptors. Severe loss-of-function can cause immunodeficiency, common variants influence autoimmune susceptibility, and partial pharmacologic inhibition is effective in inflammatory disease. This analysis covers 1,556 TYK2 variants and mutations. Of these, 84% have computational variant effect predictions. Disease context includes rheumatoid arthritis, immunodeficiency 35, and psoriasis. Example TYK2 variants include P2L, P2S, and R4C.
Variant analysis overview
- Gene: TYK2
- Protein: P29597
- UniProt accession: P29597
- Organism: Homo sapiens
- Variants analyzed: 1556
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,285 unspecified-consequence records; 1 stop retained variant; 81 synonymous variants; 151 missense variants; 18 frameshift variants; 1 in-frame insertions; 2 stop lost; 12 stop-gained variants; 1 splice-region variants; 2 in-frame deletions; 2 substitution
- Prediction scores: 1,304 variants have prediction scores (84% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: rheumatoid arthritis, immunodeficiency 35, psoriasis, psoriasis vulgaris, Crohn disease, psoriatic arthritis, COVID-19, systemic lupus erythematosus, ulcerative colitis, atopic eczema, myelofibrosis, Autosomal recessive hyper-IgE syndrome due to TYK2 deficiency.
Protein structure and variant hotspots
- Protein features: 4 domains; 2 binding sites; 7 post-translational modification sites.
- Structural context: 1,373 variants have structural context.
- PTM context: 12 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, MaveDB, LitVar.
Notable TYK2 variants
Examples include P2L, P2S, R4C, R4H, R4P, H5Q, W6*, W6G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P2L (p.Pro2Leu), TOPMed rs1285567005, gnomAD rs1285567005, REVEL 0.22, CADD 22.20
- P2S (p.Pro2Ser), TOPMed rs1004722306, gnomAD rs1004722306, REVEL 0.12, CADD 15.60, Uncertain significance, Inborn genetic diseases
- R4C (p.Arg4Cys), rs368801193, ClinGen CA9193907, ClinVar RCV001241854, ClinVar RCV004034695, REVEL 0.29, CADD 12.40, Conflicting interpretations, Inborn genetic diseases; not provided; Immunodeficiency 35
- R4H (p.Arg4His), rs12720343, ClinGen CA9193906, ClinVar RCV001231066, UniProt VAR 020597, REVEL 0.17, CADD 15.30, Uncertain significance, Immunodeficiency 35
- R4P (p.Arg4Pro), rs12720343, ClinGen CA9193905, ClinVar RCV002024935, 1000Genomes rs12720343, REVEL 0.17, CADD 17.00, Uncertain significance, Immunodeficiency 35
- H5Q (p.His5Gln), rs1218057452, ClinGen CA404023258, ClinVar RCV001772545, gnomAD rs1218057452, REVEL 0.07, CADD 0.00, Uncertain significance, not provided
- W6* (p.Trp6Ter), Ensembl rs371166091
- W6G (p.Trp6Gly), rs533026972, ClinGen CA404023254, ClinVar RCV002756609, ClinVar RCV003274026, REVEL 0.14, CADD 5.88, Uncertain significance, Inborn genetic diseases; Immunodeficiency 35
- W6R (p.Trp6Arg), rs533026972, ClinGen CA9193903, ClinVar RCV001933686, 1000Genomes rs533026972, REVEL 0.10, CADD 2.72, Uncertain significance, Immunodeficiency 35
- G7E (p.Gly7Glu), ExAC rs771091357, gnomAD rs771091357, REVEL 0.13, CADD 14.80
- M8I (p.Met8Ile), TOPMed rs995711325, gnomAD rs995711325, REVEL 0.15, CADD 0.09
- M8L (p.Met8Leu), 1000Genomes rs562457260, ExAC rs562457260, TOPMed rs562457260, gnomAD rs562457260, REVEL 0.12, CADD 0.52, Uncertain significance, Inborn genetic diseases
- A9G (p.Ala9Gly), ExAC rs773382803, gnomAD rs773382803
- A9T (p.Ala9Thr), gnomAD rs1321742051, REVEL 0.25, CADD 0.00
- A9V (p.Ala9Val), ExAC rs773382803, gnomAD rs773382803, REVEL 0.19, CADD 13.30
- G11D (p.Gly11Asp), gnomAD rs900008134, REVEL 0.28, CADD 3.97
- G11V (p.Gly11Val), gnomAD rs900008134, REVEL 0.18, CADD 11.00
- S12G (p.Ser12Gly), rs2042247201, ClinGen CA404023187, ClinVar RCV001047343, Ensembl rs2042247201, AlphaMissense 0.06, MetaLR 0.34, Uncertain significance, Immunodeficiency 35
- S12R (p.Ser12Arg), rs769741671, ClinGen CA9193899, ClinVar RCV001064932, ExAC rs769741671, REVEL 0.24, CADD 9.37, Uncertain significance, Immunodeficiency 35
- P14S (p.Pro14Ser), Ensembl rs2042247046
- V15A (p.Val15Ala), rs144960992, ClinGen CA9193896, cosmic curated COSV53392, ClinVar RCV000482893, REVEL 0.10, CADD 0.75, Benign/Likely benign, not provided; Immunodeficiency 35
- V15F (p.Val15Phe), rs374780145, ClinGen CA404023165, ClinVar RCV000696218, ESP rs374780145, REVEL 0.18, CADD 1.51, Uncertain significance, Immunodeficiency 35
- V15I (p.Val15Ile), rs374780145, ClinGen CA9193897, ClinVar RCV001887403, ESP rs374780145, REVEL 0.07, CADD 0.35, Uncertain significance, Immunodeficiency 35
- D17G (p.Asp17Gly), ExAC rs778732100, gnomAD rs778732100, REVEL 0.08, CADD 10.70
- A19T (p.Ala19Thr), rs755381338, ClinGen CA305220345, ClinVar RCV001346268, Ensembl rs755381338, REVEL 0.03, CADD 5.54, Uncertain significance, Immunodeficiency 35
- A19V (p.Ala19Val), Ensembl rs1051345509
- Q20P (p.Gln20Pro), rs753407156, ClinGen CA9193892, ClinVar RCV002573085, ExAC rs753407156, REVEL 0.27, CADD 18.20, Uncertain significance, Immunodeficiency 35
- Q20R (p.Gln20Arg), ExAC rs753407156, TOPMed rs753407156, gnomAD rs753407156, REVEL 0.07, CADD 16.90, Uncertain significance
- M22R (p.Met22Arg), Ensembl rs1599370160, REVEL 0.07, CADD 16.30, Uncertain significance
- M22T (p.Met22Thr), rs1599370160, ClinGen CA404023123, ClinVar RCV002898464, Ensembl rs1599370160, REVEL 0.05, CADD 9.07, Uncertain significance, Inborn genetic diseases
- M22V (p.Met22Val), rs777395821, ClinGen CA9193891, ClinVar RCV000645224, ExAC rs777395821, REVEL 0.07, CADD 0.29, Uncertain significance, Immunodeficiency 35
- A24T (p.Ala24Thr), Ensembl rs2042245924
- M25I (p.Met25Ile), TOPMed rs1388609058
- M25V (p.Met25Val), ExAC rs755570432, gnomAD rs755570432, REVEL 0.03, CADD 0.35
- G27D (p.Gly27Asp), rs753473919, ClinGen CA305220275, ClinVar RCV000706784, Ensembl rs753473919, REVEL 0.37, CADD 23.20, Uncertain significance, Immunodeficiency 35
- K29Q (p.Lys29Gln), ExAC rs752684154, TOPMed rs752684154, gnomAD rs752684154, REVEL 0.09, CADD 15.20
- A35T (p.Ala35Thr), TOPMed rs1335649847, REVEL 0.06, CADD 17.90
- P37L (p.Pro37Leu), cosmic curated COSV10510, gnomAD rs978916286
- P37R (p.Pro37Arg), gnomAD rs978916286, REVEL 0.24, CADD 18.20
- G39S (p.Gly39Ser), rs201283990, ClinGen CA9193886, cosmic curated COSV53386, ClinVar RCV001459985, REVEL 0.12, CADD 11.70, Likely benign, Immunodeficiency 35
- G39V (p.Gly39Val), ExAC rs766133942, TOPMed rs766133942, gnomAD rs766133942, REVEL 0.24, CADD 11.70
- G40R (p.Gly40Arg), rs763286803, ExAC rs763286803, TOPMed rs763286803, gnomAD rs763286803, REVEL 0.05, CADD 6.38, Uncertain significance, Immunodeficiency 35; not provided
- P42A (p.Pro42Ala), rs147251502, ClinGen CA9193883, ClinVar RCV001242308, ESP rs147251502, REVEL 0.06, CADD 20.40, Uncertain significance, Immunodeficiency 35
- P42H (p.Pro42His), 1000Genomes rs761736148, ExAC rs761736148, TOPMed rs761736148, gnomAD rs761736148, REVEL 0.08, CADD 20.80, Uncertain significance
- P42L (p.Pro42Leu), rs761736148, ClinGen CA9193881, ClinVar RCV001931740, 1000Genomes rs761736148, REVEL 0.10, CADD 22.00, Uncertain significance, Immunodeficiency 35
- P42T (p.Pro42Thr), rs147251502, ClinGen CA9193882, ClinVar RCV000519745, ClinVar RCV000800934, REVEL 0.05, CADD 16.80, Uncertain significance, not provided; Immunodeficiency 35
- W43G (p.Trp43Gly), Ensembl rs2042244330
- F46S (p.Phe46Ser), gnomAD rs1222690580, REVEL 0.51, CADD 23.10
- E48V (p.Glu48Val), ExAC rs777293951, gnomAD rs777293951, REVEL 0.10, CADD 19.80
- S49L (p.Ser49Leu), TOPMed rs1049998858
- S50L (p.Ser50Leu), rs747484809, ClinGen CA9193878, ClinVar RCV001238943, ExAC rs747484809, REVEL 0.09, CADD 18.80, Uncertain significance, Immunodeficiency 35
- S50P (p.Ser50Pro), TOPMed rs1387248228, gnomAD rs1387248228, REVEL 0.11, CADD 13.30
- L51P (p.Leu51Pro), TOPMed rs931666925, gnomAD rs931666925, REVEL 0.43, CADD 22.30
- L51Q (p.Leu51Gln), TOPMed rs931666925, gnomAD rs931666925, REVEL 0.41, CADD 24.70
- L51V (p.Leu51Val), gnomAD rs2042243634, REVEL 0.05, CADD 15.10
- T52I (p.Thr52Ile), TOPMed rs921579430
- T52P (p.Thr52Pro), TOPMed rs1484227289, gnomAD rs1484227289, REVEL 0.58, CADD 24.80
- A53T (p.Ala53Thr), rs55762744, ClinGen CA9193876, ClinVar RCV000441975, ClinVar RCV000534611, REVEL 0.46, CADD 24.60, Benign, not specified; not provided; Immunodeficiency 35
- C57S (p.Cys57Ser), TOPMed rs2042242880, gnomAD rs2042242880, REVEL 0.67, CADD 24.60
- I60L (p.Ile60Leu), ExAC rs755663053, TOPMed rs755663053, gnomAD rs755663053, Uncertain significance
- I60T (p.Ile60Thr), rs752152984, ClinGen CA9193872, ClinVar RCV001344387, ExAC rs752152984, REVEL 0.36, CADD 16.60, Uncertain significance, Immunodeficiency 35
- I60V (p.Ile60Val), ExAC rs755663053, TOPMed rs755663053, gnomAD rs755663053, REVEL 0.06, CADD 1.14, Uncertain significance, Inborn genetic diseases
- A61P (p.Ala61Pro), Ensembl rs2145370916
- H62Y (p.His62Tyr), TOPMed rs1434247208, gnomAD rs1434247208, REVEL 0.06, CADD 16.40
- K63E (p.Lys63Glu), rs1249291887, ClinGen CA404022615, ClinVar RCV001313453, ClinVar RCV006391890, REVEL 0.10, CADD 15.70, Uncertain significance, Inborn genetic diseases; Immunodeficiency 35
- V64A (p.Val64Ala), TOPMed rs1399398857, gnomAD rs1399398857, REVEL 0.24, CADD 16.70
- T67I (p.Thr67Ile), ExAC rs774905892, TOPMed rs774905892, gnomAD rs774905892, REVEL 0.40, CADD 25.20, Uncertain significance
- T67P (p.Thr67Pro), Ensembl rs1599356131
- T67S (p.Thr67Ser), rs774905892, ClinGen CA9193812, ClinVar RCV001042380, ExAC rs774905892, REVEL 0.12, CADD 18.90, Uncertain significance, Immunodeficiency 35
- P68A (p.Pro68Ala), rs1045396233, ClinGen CA404020580, ClinVar RCV002001705, Ensembl rs1045396233, AlphaMissense 0.18, MetaLR 0.22, Uncertain significance, Immunodeficiency 35
- P68T (p.Pro68Thr), Ensembl rs1045396233, Uncertain significance
- F71L (p.Phe71Leu), rs374071090, ClinGen CA9193811, ClinVar RCV000645233, ESP rs374071090, REVEL 0.11, CADD 18.80, Uncertain significance, Immunodeficiency 35
- L73F (p.Leu73Phe), cosmic curated COSV53390, TOPMed rs2041763923, gnomAD rs2041763923, REVEL 0.67, CADD 24.70
- A75D (p.Ala75Asp), 1000Genomes rs150861764, ESP rs150861764, ExAC rs150861764, gnomAD rs150861764
- A75S (p.Ala75Ser), Ensembl rs2041763574
- A75V (p.Ala75Val), 1000Genomes rs150861764, ESP rs150861764, ExAC rs150861764, gnomAD rs150861764, REVEL 0.72, CADD 27.10
- D78N (p.Asp78Asn), rs778171865, ClinGen CA9193805, ClinVar RCV001368942, ExAC rs778171865, REVEL 0.07, AlphaMissense 0.13, Uncertain significance, Immunodeficiency 35
- D78Y (p.Asp78Tyr), rs778171865, ClinGen CA404020360, ClinVar RCV001210453, ExAC rs778171865, AlphaMissense 0.13, MetaLR 0.09, Uncertain significance, Immunodeficiency 35
- A79V (p.Ala79Val), gnomAD rs1420420519, REVEL 0.04, CADD 16.60
- Q80H (p.Gln80His), TOPMed rs972420234, gnomAD rs972420234, REVEL 0.04, CADD 18.60
- A81S (p.Ala81Ser), ExAC rs752941433, TOPMed rs752941433, gnomAD rs752941433, REVEL 0.03, CADD 17.30
- A81T (p.Ala81Thr), ExAC rs752941433, TOPMed rs752941433, gnomAD rs752941433, REVEL 0.08, CADD 18.20
- A81V (p.Ala81Val), rs1049619, UniProt VAR 037797, Ensembl rs1049619, AlphaMissense 0.13, MetaLR 0.27
- Q82* (p.Gln82Ter), gnomAD rs1163009373, CADD 35.00
- V83A (p.Val83Ala), rs1407281800, ClinGen CA404020245, ClinVar RCV001936082, TOPMed rs1407281800, REVEL 0.14, CADD 22.90, Uncertain significance, Immunodeficiency 35
- V83I (p.Val83Ile), Ensembl rs2041762478
- W84* (p.Trp84Ter), gnomAD rs1224824249, CADD 36.00
- P86S (p.Pro86Ser), ESP rs141466711, ExAC rs141466711, TOPMed rs141466711, gnomAD rs141466711, REVEL 0.23, CADD 21.50, Uncertain significance
- P86T (p.Pro86Thr), rs141466711, ClinGen CA9193802, ClinVar RCV000645235, ESP rs141466711, REVEL 0.62, CADD 25.00, Uncertain significance, Immunodeficiency 35
- P87L (p.Pro87Leu), rs2145275752, ClinGen CA404020161, ClinVar RCV001998415, Ensembl rs2145275752, REVEL 0.80, CADD 28.70, Uncertain significance, Immunodeficiency 35
- N88D (p.Asn88Asp), rs752013617, ClinGen CA9193800, ClinVar RCV002643305, ExAC rs752013617, REVEL 0.45, CADD 25.80, Uncertain significance, Immunodeficiency 35
- I90T (p.Ile90Thr), gnomAD rs1490056740, REVEL 0.07, CADD 15.30
- I93F (p.Ile93Phe), rs1434718123, ClinGen CA404020055, ClinVar RCV001323474, ClinVar RCV003166889, REVEL 0.25, CADD 16.90, Uncertain significance, Inborn genetic diseases; Immunodeficiency 35
- P94L (p.Pro94Leu), ExAC rs765557425, gnomAD rs765557425, Uncertain significance
- P94R (p.Pro94Arg), rs765557425, ClinGen CA404020033, ClinVar RCV001295736, ExAC rs765557425, REVEL 0.09, CADD 16.90, Uncertain significance, Immunodeficiency 35
- R95K (p.Arg95Lys), rs1599355965, ClinGen CA404020023, ClinVar RCV000812810, Ensembl rs1599355965, AlphaMissense 0.09, MetaLR 0.14, Uncertain significance, Immunodeficiency 35
- D96Y (p.Asp96Tyr), rs2145275479, ClinGen CA404020013, ClinVar RCV001977894, Ensembl rs2145275479, AlphaMissense 0.13, MetaLR 0.44, Uncertain significance, Immunodeficiency 35
- A97T (p.Ala97Thr), Ensembl rs2041760993, REVEL 0.05, CADD 0.03
- L99P (p.Leu99Pro), cosmic curated COSV10636, ExAC rs775200017, TOPMed rs775200017, gnomAD rs775200017, REVEL 0.53, CADD 22.50
- L101I (p.Leu101Ile), rs1001433036, gnomAD 19-10350966-G-T, CADD 13.10
- Y102C (p.Tyr102Cys), Ensembl rs1599355950
- R104C (p.Arg104Cys), cosmic curated COSV10729, 1000Genomes rs551925120, ExAC rs551925120, TOPMed rs551925120, REVEL 0.71, CADD 24.00, Uncertain significance, Inborn genetic diseases
- R104H (p.Arg104His), rs774448680, ClinGen CA9193791, cosmic curated COSV53386, ClinVar RCV000522191, REVEL 0.81, CADD 25.40, Uncertain significance, not provided; Immunodeficiency 35
- I105M (p.Ile105Met), ExAC rs770951647, TOPMed rs770951647, gnomAD rs770951647, Likely benign, Inborn genetic diseases
- I105V (p.Ile105Val), TOPMed rs1029569489, gnomAD rs1029569489, REVEL 0.06, CADD 22.50
- R106T (p.Arg106Thr), ExAC rs749206339, gnomAD rs749206339, REVEL 0.81, CADD 34.00
- R110Q (p.Arg110Gln), rs56090991, ClinGen CA9193762, ClinVar RCV001122035, ExAC rs56090991, REVEL 0.38, CADD 24.10, Uncertain significance, Immunodeficiency 35
- R110W (p.Arg110Trp), rs747918278, ClinGen CA9193763, cosmic curated COSV53389, ClinVar RCV001122036, REVEL 0.61, CADD 32.00, Uncertain significance, Immunodeficiency 35
- N111K (p.Asn111Lys), rs2041753647, ClinGen CA404019221, ClinVar RCV001209836, Ensembl rs2041753647, REVEL 0.59, CADD 23.80, Uncertain significance, Immunodeficiency 35
- H113Y (p.His113Tyr), rs759452764, gnomAD 19-10350903-G-A, CADD 7.52
- N116H (p.Asn116His), TOPMed rs1361836365, gnomAD rs1361836365, REVEL 0.19, CADD 24.00
- N116Y (p.Asn116Tyr), TOPMed rs1361836365, gnomAD rs1361836365, REVEL 0.26, CADD 25.50
- P117S (p.Pro117Ser), rs141864691, ClinGen CA305209442, cosmic curated COSV53389, ClinVar RCV000701408, REVEL 0.09, CADD 15.30, Uncertain significance, Immunodeficiency 35
- R118Q (p.Arg118Gln), rs369530676, ClinGen CA9193760, cosmic curated COSV10636, ClinVar RCV000761987, REVEL 0.04, CADD 15.90, Conflicting interpretations, Inborn genetic diseases; Immunodeficiency 35; not provided
- R118W (p.Arg118Trp), rs138742402, ClinGen CA9193761, ClinVar RCV003004952, ClinVar RCV003898685, REVEL 0.14, CADD 25.40, Uncertain significance, Immunodeficiency 35
- E119K (p.Glu119Lys), gnomAD 19-10350951-C-T, CADD 15.20
- P120L (p.Pro120Leu), rs758463317, ClinGen CA9193758, ClinVar RCV001307862, ClinVar RCV003166753, REVEL 0.15, CADD 22.50, Uncertain significance, Inborn genetic diseases; Immunodeficiency 35
- P120Q (p.Pro120Gln), ExAC rs758463317, TOPMed rs758463317, gnomAD rs758463317, REVEL 0.16, CADD 19.40, Uncertain significance
- P120S (p.Pro120Ser), 1000Genomes rs199807224, ExAC rs199807224, TOPMed rs199807224, gnomAD rs199807224, REVEL 0.08, CADD 20.50
- A121S (p.Ala121Ser), ExAC rs779331912, TOPMed rs779331912, gnomAD rs779331912
- A121T (p.Ala121Thr), cosmic curated COSV10608, ExAC rs779331912, TOPMed rs779331912, gnomAD rs779331912, REVEL 0.05, CADD 10.50
- V122G (p.Val122Gly), Ensembl rs78529614
- V122M (p.Val122Met), TOPMed rs1238838283, gnomAD rs1238838283, REVEL 0.34, CADD 24.60
- V122F (p.Val122Phe), rs756965030, gnomAD 19-10350930-C-A, CADD 2.36
- V122I (p.Val122Ile), rs756965030, gnomAD 19-10350930-C-T, CADD 3.03
- Y123S (p.Tyr123Ser), Ensembl rs1599355641
- R124C (p.Arg124Cys), rs757581005, ClinGen CA9193755, ClinVar RCV001122034, ClinVar RCV003163276, REVEL 0.73, CADD 32.00, Uncertain significance, Immunodeficiency 35; Inborn genetic diseases
- R124H (p.Arg124His), TOPMed rs542503483, gnomAD rs542503483, REVEL 0.72, CADD 27.60
- R124* (p.Arg124Ter), rs752249209, gnomAD 19-10350912-G-A, CADD 6.40
- R124G (p.Arg124Gly), gnomAD 19-10350936-T-C, CADD 2.38
- R124W (p.Arg124Trp), rs920085264, Uncertain significance
- C125F (p.Cys125Phe), Ensembl rs2145273488, REVEL 0.20, CADD 16.30
- C125R (p.Cys125Arg), rs2145273513, ClinGen CA404019103, ClinVar RCV001994402, Ensembl rs2145273513, AlphaMissense 0.15, MetaLR 0.17, Uncertain significance, Immunodeficiency 35
- G126S (p.Gly126Ser), gnomAD 19-10350933-C-T, CADD 2.91
- P127L (p.Pro127Leu), gnomAD rs1308616286, REVEL 0.04, CADD 17.70
- P128S (p.Pro128Ser), TOPMed rs1013930418, REVEL 0.05, CADD 18.40
- P128T (p.Pro128Thr), rs2040768270, gnomAD 19-10350921-G-T, CADD 1.93
- P128A (p.Pro128Ala), gnomAD 19-10350921-G-C, CADD 2.04
- E131K (p.Glu131Lys), ExAC rs754709072, TOPMed rs754709072, gnomAD rs754709072, REVEL 0.03, CADD 7.28
- A132V (p.Ala132Val), TOPMed rs2041750912, REVEL 0.05, CADD 13.30
- S133F (p.Ser133Phe), Ensembl rs267605274
- S133P (p.Ser133Pro), ExAC rs751242030, gnomAD rs751242030, REVEL 0.11, CADD 10.10
- D135N (p.Asp135Asn), rs755452263, gnomAD 19-10350939-C-T, CADD 5.10
- Q136H (p.Gln136His), ExAC rs762486838, TOPMed rs762486838, gnomAD rs762486838, REVEL 0.06, CADD 8.07
- Q136K (p.Gln136Lys), rs766052825, ClinGen CA9193750, ClinVar RCV001864505, ExAC rs766052825, REVEL 0.12, CADD 4.88, Uncertain significance, Immunodeficiency 35
- T137R (p.Thr137Arg), ESP rs149044054, ExAC rs149044054, TOPMed rs149044054, gnomAD rs149044054, REVEL 0.05, CADD 9.62
- Q139R (p.Gln139Arg), TOPMed rs2041749897, REVEL 0.06, CADD 11.50
- M141T (p.Met141Thr), rs2041749425, ClinGen CA404018904, ClinVar RCV003628231, TOPMed rs2041749425, REVEL 0.12, CADD 5.87, Uncertain significance, Immunodeficiency 35
- L143F (p.Leu143Phe), TOPMed rs887883177, gnomAD rs887883177, REVEL 0.22, CADD 15.70
- L143P (p.Leu143Pro), ExAC rs761545778, TOPMed rs761545778, gnomAD rs761545778, REVEL 0.69, CADD 29.00
- L143V (p.Leu143Val), rs1296974908, gnomAD 19-10350915-G-C, CADD 1.10
- P146L (p.Pro146Leu), rs137904701, ClinGen CA9193743, ClinVar RCV000802854, ClinVar RCV003413607, REVEL 0.11, CADD 20.70, Uncertain significance, TYK2-related disorder; Immunodeficiency 35
- A147D (p.Ala147Asp), ESP rs150331673, ExAC rs150331673, TOPMed rs150331673, gnomAD rs150331673, REVEL 0.38, CADD 24.00
- A147V (p.Ala147Val), cosmic curated COSV99315, ESP rs150331673, ExAC rs150331673, TOPMed rs150331673, REVEL 0.31, CADD 26.40
- F149I (p.Phe149Ile), TOPMed rs2041748095
- F149S (p.Phe149Ser), TOPMed rs1394628611, REVEL 0.68, CADD 32.00, Uncertain significance, not provided
- E150A (p.Glu150Ala), ESP rs200718118, ExAC rs200718118, TOPMed rs200718118, gnomAD rs200718118, REVEL 0.40, CADD 28.80, Uncertain significance
- E150G (p.Glu150Gly), rs200718118, ClinGen CA9193741, ClinVar RCV000820314, ClinVar RCV003362977, REVEL 0.48, CADD 32.00, Uncertain significance, Inborn genetic diseases; Immunodeficiency 35
- E150K (p.Glu150Lys), TOPMed rs1391138496, gnomAD rs1391138496, REVEL 0.47, CADD 28.00
- L152F (p.Leu152Phe), ExAC rs745894180, TOPMed rs745894180, gnomAD rs745894180, REVEL 0.34, CADD 25.80
- L152R (p.Leu152Arg), gnomAD rs1355892968, REVEL 0.69, CADD 29.70
- L152V (p.Leu152Val), ExAC rs745894180, TOPMed rs745894180, gnomAD rs745894180, REVEL 0.25, CADD 26.90
- E154* (p.Glu154Ter), rs879253731, ClinGen CA10575998, ClinVar RCV000210466, Ensembl rs879253731, CADD 37.00, Pathogenic
- E154X, rs879253731, Pathogenic
- G156C (p.Gly156Cys), Ensembl rs2145259861
- K157E (p.Lys157Glu), Ensembl rs956505107, REVEL 0.25, CADD 24.30
- H158R (p.His158Arg), ExAC rs770297599, TOPMed rs770297599, gnomAD rs770297599, REVEL 0.13, CADD 21.30
- F160L (p.Phe160Leu), Ensembl rs2145259750
- D163N (p.Asp163Asn), TOPMed rs896099330
- V164L (p.Val164Leu), rs531355933, ClinGen CA9193711, ClinVar RCV001299251, 1000Genomes rs531355933, REVEL 0.10, CADD 15.50, Uncertain significance, Immunodeficiency 35
- V164M (p.Val164Met), rs531355933, ClinGen CA9193712, cosmic curated COSV53389, ClinVar RCV001370170, REVEL 0.17, CADD 22.20, Uncertain significance, Immunodeficiency 35
- A165T (p.Ala165Thr), rs370420133, ClinGen CA9193710, ClinVar RCV001127809, ESP rs370420133, REVEL 0.18, CADD 22.50, Uncertain significance, Immunodeficiency 35
- L167P (p.Leu167Pro), gnomAD rs1421177533, REVEL 0.71, CADD 26.30
- L167R (p.Leu167Arg), gnomAD rs1421177533, REVEL 0.69, CADD 25.90
- W168R (p.Trp168Arg), Ensembl rs2145259477
- E169G (p.Glu169Gly), TOPMed rs1478105936, gnomAD rs1478105936, REVEL 0.12, CADD 24.20
- E169K (p.Glu169Lys), rs778545468, ClinGen CA9193709, ClinVar RCV001127807, ExAC rs778545468, REVEL 0.07, CADD 21.70, Uncertain significance, Immunodeficiency 35
- S171L (p.Ser171Leu), cosmic curated COSV10959, ExAC rs756721201, TOPMed rs756721201, gnomAD rs756721201, REVEL 0.13, CADD 19.60
- S171T (p.Ser171Thr), Ensembl rs2145259361
- T172I (p.Thr172Ile), gnomAD rs1216286893, REVEL 0.07, CADD 11.30
Public TYK2 analysis runs
- TYK2 analysis run — TYK2 (1,556 variants) — completed 2026-08-19