JAK3 (Tyrosine-protein kinase JAK3) variants and mutations
JAK3 (also known as Tyrosine-protein kinase JAK3) is a human protein-coding gene encoding a tyrosine-protein kinase protein. It carries signals from cytokine receptors using the common gamma chain and is essential for T-cell and NK-cell development. Biallelic loss-of-function variants cause severe combined immunodeficiency, while activating somatic variants occur in selected leukemias and lymphomas. This analysis covers 2,778 JAK3 variants and mutations. Of these, 53% have computational variant effect predictions. Disease context includes T-B+ severe combined immunodeficiency due to JAK3 deficiency, ulcerative colitis, and rheumatoid arthritis. Example JAK3 variants include M1?, A2P, and A2T.
Variant analysis overview
- Gene: JAK3
- Protein: Tyrosine-protein kinase JAK3
- UniProt accession: P52333
- Organism: Homo sapiens
- Variants analyzed: 2778
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 2,541 unspecified-consequence records; 4 stop lost; 12 frameshift variants; 66 synonymous variants; 128 missense variants; 3 in-frame deletions; 15 stop-gained variants; 1 stop retained variant; 3 splice-region variants; 5 substitution
- Prediction scores: 1,471 variants have prediction scores (53% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: T-B+ severe combined immunodeficiency due to JAK3 deficiency, ulcerative colitis, rheumatoid arthritis, myelofibrosis, atopic eczema, alopecia areata, psoriatic arthritis, Crohn disease, acquired polycythemia vera, severe combined immunodeficiency, graft versus host disease, Eczematoid dermatitis.
Protein structure and variant hotspots
- Protein features: 4 domains; 2 binding sites; 6 post-translational modification sites.
- Structural context: 2,401 variants have structural context.
- PTM context: 19 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 JAK3 variants
Examples include M1?, A2P, A2T, A2V, P3L, P3S, S5G, S5N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A2P (p.Ala2Pro), rs2147701252, ClinGen CA404775622, ClinVar RCV003066107, AlphaMissense 0.16, MetaLR 0.34, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- A2T (p.Ala2Thr), Ensembl rs2147701252, REVEL 0.24, AlphaMissense 0.16
- A2V (p.Ala2Val), rs1568408509, ClinGen CA404775614, ClinVar RCV000706025, TOPMed rs1568408509, REVEL 0.18, CADD 21.30, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- P3L (p.Pro3Leu), ExAC rs766883331, gnomAD rs766883331, REVEL 0.39, CADD 26.40
- P3S (p.Pro3Ser), Ensembl rs2147701242
- S5G (p.Ser5Gly), ExAC rs773632633, TOPMed rs773632633, gnomAD rs773632633, REVEL 0.14, CADD 4.57
- S5N (p.Ser5Asn), rs566269022, ClinGen CA9302285, ClinVar RCV001038374, 1000Genomes rs566269022, REVEL 0.20, CADD 2.47, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- S5R (p.Ser5Arg), cosmic curated COSV10471
- E6Q (p.Glu6Gln), TOPMed rs2094247449
- E7D (p.Glu7Asp), TOPMed rs1488831072, NCI-TCGA Cosmic COSV7168, cosmic curated COSV71685, Variant assessed as somatic; moderate impact.
- T8M (p.Thr8Met), rs145500023, ClinGen CA160231, ClinVar RCV000121264, ClinVar RCV000639632, REVEL 0.29, CADD 22.90, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- T8R (p.Thr8Arg), 1000Genomes rs145500023, ESP rs145500023, ExAC rs145500023, TOPMed rs145500023, REVEL 0.34, CADD 22.80, Uncertain significance
- P9L (p.Pro9Leu), gnomAD rs1400025357
- P9S (p.Pro9Ser), rs774076800, NCI-TCGA Cosmic COSV1015, cosmic curated COSV10151, ExAC rs774076800, AlphaMissense 0.33, MetaLR 0.53, Variant assessed as somatic; moderate impact.
- L10M (p.Leu10Met), cosmic curated COSV71688
- L10P (p.Leu10Pro), cosmic curated COSV10594, Ensembl rs2147701171
- L10V (p.Leu10Val), rs1052019264, ClinGen CA306142625, cosmic curated COSV71686, ClinVar RCV000639634, REVEL 0.32, CADD 20.80, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- I11V (p.Ile11Val), gnomAD rs1436664792, REVEL 0.26, CADD 19.60
- P12L (p.Pro12Leu), rs56061056, ClinGen CA9302282, ClinVar RCV000306819, UniProt VAR 041722, REVEL 0.20, CADD 16.90, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- P12S (p.Pro12Ser), cosmic curated COSV71685, gnomAD rs1423714862, REVEL 0.18, CADD 0.47
- Q13* (p.Gln13Ter), rs201771231, NCI-TCGA Cosmic COSV7168, cosmic curated COSV71686, gnomAD rs201771231, CADD 35.00, Variant assessed as somatic; high impact.
- Q13K (p.Gln13Lys), gnomAD rs201771231, REVEL 0.31, CADD 15.90
- Q13R (p.Gln13Arg), TOPMed rs200860180, REVEL 0.28, CADD 17.30
- R14C (p.Arg14Cys), rs896064879, NCI-TCGA Cosmic COSV7168, cosmic curated COSV71688, TOPMed rs896064879, REVEL 0.33, CADD 24.20, Variant assessed as somatic; moderate impact.
- R14H (p.Arg14His), rs780084832, NCI-TCGA Cosmic COSV1015, NCI-TCGA Cosmic COSV7168, cosmic curated COSV71685, REVEL 0.24, CADD 24.80, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- R14L (p.Arg14Leu), cosmic curated COSV10151
- R14S (p.Arg14Ser), NCI-TCGA Cosmic COSV7168, REVEL 0.36, CADD 24.50, Variant assessed as somatic; moderate impact.
- S15L (p.Ser15Leu), cosmic curated COSV71686, gnomAD rs1457535594, REVEL 0.32, CADD 26.10
- C16S (p.Cys16Ser), NCI-TCGA Cosmic COSV1015, cosmic curated COSV10151, NCI-TCGA Cosmic COSV7168, Variant assessed as somatic; moderate impact.
- C16Y (p.Cys16Tyr), cosmic curated COSV71686, Ensembl rs2147701122
- S17G (p.Ser17Gly), Ensembl rs1568408440, REVEL 0.37, CADD 25.10
- S17I (p.Ser17Ile), NCI-TCGA TCGA novel, TOPMed rs2094247284, Variant assessed as somatic; moderate impact.
- S17N (p.Ser17Asn), cosmic curated COSV10594
- S17T (p.Ser17Thr), TOPMed rs2094247284, REVEL 0.28, CADD 24.70
- L19F (p.Leu19Phe), ExAC rs781178874, gnomAD rs781178874, REVEL 0.24, CADD 0.01
- L19S (p.Leu19Ser), ExAC rs745658193, gnomAD rs745658193, REVEL 0.13, CADD 15.80
- S20F (p.Ser20Phe), cosmic curated COSV71685
- S20P (p.Ser20Pro), cosmic curated COSV71686, 1000Genomes rs199773433, ExAC rs199773433, TOPMed rs199773433, Uncertain significance
- S20T (p.Ser20Thr), rs199773433, ClinGen CA160237, ClinVar RCV000121266, ClinVar RCV004019683, REVEL 0.28, CADD 24.20, Uncertain significance, Inborn genetic diseases
- T21M (p.Thr21Met), rs752820429, ClinGen CA9302277, cosmic curated COSV71686, ClinVar RCV001301284, REVEL 0.17, CADD 18.60, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- T21S (p.Thr21Ser), Ensembl rs2147701085
- E22K (p.Glu22Lys), cosmic curated COSV10535, TOPMed rs200065012, gnomAD rs200065012
- E22Q (p.Glu22Gln), TOPMed rs200065012, gnomAD rs200065012, REVEL 0.25, CADD 24.10
- A23D (p.Ala23Asp), NCI-TCGA Cosmic COSV1015, cosmic curated COSV10151, Variant assessed as somatic; moderate impact.
- A23G (p.Ala23Gly), Ensembl rs2147701058
- A23S (p.Ala23Ser), ExAC rs753974832, TOPMed rs753974832, gnomAD rs753974832, REVEL 0.23, CADD 14.30
- A23T (p.Ala23Thr), cosmic curated COSV10594
- A23V (p.Ala23Val), Ensembl rs2147701058
- G24A (p.Gly24Ala), cosmic curated COSV71686
- G24D (p.Gly24Asp), ExAC rs766866864, gnomAD rs766866864, REVEL 0.22, CADD 20.30, Uncertain significance, Inborn genetic diseases
- A25P (p.Ala25Pro), ExAC rs761209690, gnomAD rs761209690, REVEL 0.30, CADD 16.60
- A25T (p.Ala25Thr), ExAC rs761209690, gnomAD rs761209690, REVEL 0.16, CADD 9.53
- A25V (p.Ala25Val), NCI-TCGA Cosmic COSV7168, cosmic curated COSV71688, REVEL 0.09, CADD 15.60, Variant assessed as somatic; moderate impact.
- L26M (p.Leu26Met), cosmic curated COSV10594
- H27N (p.His27Asn), cosmic curated COSV71688
- H27Q (p.His27Gln), rs1039181282, ClinGen CA306142410, ClinVar RCV000553899, TOPMed rs1039181282, REVEL 0.18, CADD 0.00, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- H27R (p.His27Arg), TOPMed rs1321875586, gnomAD rs1321875586, REVEL 0.26, CADD 17.20
- H27Y (p.His27Tyr), Ensembl rs2147701031
- V28G (p.Val28Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V28L (p.Val28Leu), cosmic curated COSV71686
- V28M (p.Val28Met), cosmic curated COSV10471
- P31L (p.Pro31Leu), cosmic curated COSV71688
- P31S (p.Pro31Ser), Ensembl rs2147701006
- P31T (p.Pro31Thr), cosmic curated COSV10471
- A32T (p.Ala32Thr), rs587778416, ClinGen CA160234, ClinVar RCV000121265, TOPMed rs587778416, REVEL 0.07, CADD 8.41, not provided, not specified
- R33L (p.Arg33Leu), cosmic curated COSV71687
- R33Q (p.Arg33Gln), ExAC rs768370832, TOPMed rs768370832, gnomAD rs768370832, REVEL 0.27, CADD 16.90, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- R33W (p.Arg33Trp), cosmic curated COSV71685, ExAC rs565783591, TOPMed rs565783591, gnomAD rs565783591, REVEL 0.40, CADD 22.70, Uncertain significance, Inborn genetic diseases
- G34A (p.Gly34Ala), rs2514582341, ClinGen CA2739276610, ClinVar RCV003621968, Pathogenic
- P35L (p.Pro35Leu), rs200740037, ExAC rs200740037, gnomAD rs200740037, REVEL 0.27, CADD 21.30, Variant assessed as somatic; moderate impact.
- G36E (p.Gly36Glu), TOPMed rs2094247065
- G36R (p.Gly36Arg), rs769828760, ClinGen CA9302264, cosmic curated COSV71687, ClinVar RCV002785242, REVEL 0.35, CADD 18.50, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- P37A (p.Pro37Ala), cosmic curated COSV71685, TOPMed rs955716335, gnomAD rs955716335, REVEL 0.14, CADD 15.20, Uncertain significance
- P37H (p.Pro37His), ExAC rs200960683, TOPMed rs200960683, gnomAD rs200960683, Uncertain significance
- P37L (p.Pro37Leu), ExAC rs200960683, TOPMed rs200960683, gnomAD rs200960683, REVEL 0.18, CADD 19.70, Uncertain significance
- P37R (p.Pro37Arg), rs200960683, ClinGen CA9302263, ClinVar RCV001304055, ExAC rs200960683, REVEL 0.20, CADD 22.60, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- P37S (p.Pro37Ser), TOPMed rs955716335, gnomAD rs955716335, REVEL 0.12, CADD 15.30, Uncertain significance
- P37T (p.Pro37Thr), rs955716335, ClinGen CA404775238, ClinVar RCV003621944, TOPMed rs955716335, REVEL 0.15, CADD 15.60, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- P38S (p.Pro38Ser), Ensembl rs2147700946
- Q39E (p.Gln39Glu), rs2514582265, ClinGen CA404775217, ClinVar RCV002810365, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- Q39P (p.Gln39Pro), Ensembl rs1599881465
- R40C (p.Arg40Cys), rs140784576, NCI-TCGA Cosmic COSV7168, cosmic curated COSV71686, ESP rs140784576, REVEL 0.20, CADD 8.39, Variant assessed as somatic; moderate impact.
- R40H (p.Arg40His), rs56384680, ClinGen CA9302261, cosmic curated COSV71685, ClinVar RCV000530161, REVEL 0.05, CADD 14.20, Conflicting interpretations, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- L41I (p.Leu41Ile), cosmic curated COSV10151
- L41V (p.Leu41Val), Ensembl rs2147700910
- S42F (p.Ser42Phe), Ensembl rs2094246939, Uncertain significance
- S42Y (p.Ser42Tyr), rs2094246939, ClinGen CA404775180, ClinVar RCV001041840, Ensembl rs2094246939, AlphaMissense 0.15, MetaLR 0.37, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- F43L (p.Phe43Leu), TOPMed rs2094246932, REVEL 0.26, CADD 22.60
- S44F (p.Ser44Phe), rs201650430, cosmic curated COSV71685, ClinGen CA9302260, REVEL 0.10, CADD 20.50, Uncertain significance, Inborn genetic diseases
- F45L (p.Phe45Leu), gnomAD rs1226305304, REVEL 0.25, CADD 22.60, Uncertain significance, Inborn genetic diseases
- F45S (p.Phe45Ser), Ensembl rs916019, REVEL 0.38, CADD 19.30
- G46E (p.Gly46Glu), gnomAD rs1284042750
- G46R (p.Gly46Arg), rs778988303, ClinGen CA9302259, ClinVar RCV001038232, ExAC rs778988303, REVEL 0.49, CADD 32.00, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- D47E (p.Asp47Glu), rs1599881400, ClinGen CA404775118, ClinVar RCV000813663, Ensembl rs1599881400, REVEL 0.05, CADD 9.69, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- D47G (p.Asp47Gly), ExAC rs755294746, TOPMed rs755294746, gnomAD rs755294746, REVEL 0.17, CADD 22.70
- D47N (p.Asp47Asn), cosmic curated COSV10535, Ensembl rs2094246893
- D47Y (p.Asp47Tyr), NCI-TCGA Cosmic COSV7168, cosmic curated COSV71686, Ensembl rs2094246893, REVEL 0.19, CADD 23.70, Variant assessed as somatic; moderate impact.
- H48Q (p.His48Gln), TOPMed rs1455932507
- L49V (p.Leu49Val), NCI-TCGA Cosmic COSV7168, cosmic curated COSV71686, Variant assessed as somatic; moderate impact.
- A50G (p.Ala50Gly), TOPMed rs2094246856
- A50P (p.Ala50Pro), gnomAD rs1363017670, REVEL 0.73, CADD 26.50
- A50S (p.Ala50Ser), NCI-TCGA TCGA novel, REVEL 0.47, CADD 25.40, Variant assessed as somatic; moderate impact.
- A50V (p.Ala50Val), TOPMed rs2094246856
- E51* (p.Glu51Ter), cosmic curated COSV71685, CADD 39.00
- E51D (p.Glu51Asp), cosmic curated COSV71688, REVEL 0.55, CADD 23.80
- E51K (p.Glu51Lys), cosmic curated COSV10753
- D52A (p.Asp52Ala), TOPMed rs943912652
- D52E (p.Asp52Glu), cosmic curated COSV71687, REVEL 0.16, CADD 1.19
- D52G (p.Asp52Gly), TOPMed rs943912652, REVEL 0.30, CADD 24.60
- D52N (p.Asp52Asn), rs2147700846, ClinGen CA404775063, ClinVar RCV001369383, Ensembl rs2147700846, AlphaMissense 0.10, MetaLR 0.20, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- D52V (p.Asp52Val), TOPMed rs943912652
- L53M (p.Leu53Met), TOPMed rs1296361489, gnomAD rs1296361489, REVEL 0.39, CADD 22.90
- L53P (p.Leu53Pro), Ensembl rs2147700827
- C54W (p.Cys54Trp), TOPMed rs200626608, gnomAD rs200626608, Likely benign
- V55G (p.Val55Gly), Ensembl rs2147700792
- V55L (p.Val55Leu), NCI-TCGA Cosmic COSV1015, cosmic curated COSV10151, REVEL 0.28, CADD 23.20, Variant assessed as somatic; moderate impact.
- V55M (p.Val55Met), rs749334592, ClinGen CA9302257, NCI-TCGA Cosmic COSV1015, ClinVar RCV002639470, REVEL 0.36, CADD 23.50, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- Q56* (p.Gln56Ter), Ensembl rs2147700780, CADD 35.00
- Q56H (p.Gln56His), cosmic curated COSV71686, REVEL 0.09, CADD 8.42
- Q56R (p.Gln56Arg), Ensembl rs2147700769
- A57P (p.Ala57Pro), Ensembl rs2147700763, REVEL 0.58, CADD 27.40
- A57S (p.Ala57Ser), cosmic curated COSV71686, REVEL 0.42, CADD 26.00
- A58T (p.Ala58Thr), rs2046340891, ClinGen CA404774979, ClinVar RCV001976801, Ensembl rs2046340891, REVEL 0.65, CADD 27.40, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- A58G (p.Ala58Gly), Ensembl rs2147700747
- A58V (p.Ala58Val), Ensembl rs2147700747, REVEL 0.65, CADD 27.80
- K59* (p.Lys59Ter), rs2514582034, ClinGen CA404774961, ClinVar RCV002797190, CADD 40.00, Likely pathogenic
- K59N (p.Lys59Asn), Ensembl rs2147700734, REVEL 0.45, CADD 24.50
- A60T (p.Ala60Thr), ExAC rs780157263, gnomAD rs780157263, REVEL 0.23, CADD 22.50
- S61C (p.Ser61Cys), cosmic curated COSV10753, Ensembl rs2147700727
- S61G (p.Ser61Gly), Ensembl rs2147700727
- S61R (p.Ser61Arg), 1000Genomes rs200269517, ExAC rs200269517, TOPMed rs200269517, gnomAD rs200269517, REVEL 0.36, CADD 17.80, Uncertain significance
- G62S (p.Gly62Ser), rs199602590, ClinGen CA9302254, cosmic curated COSV71686, ClinVar RCV001224740, REVEL 0.29, CADD 26.70, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- G62V (p.Gly62Val), TOPMed rs1252777378
- I63M (p.Ile63Met), cosmic curated COSV71688, Ensembl rs2094245890
- I63V (p.Ile63Val), rs144405201, ClinGen CA9302225, cosmic curated COSV10611, ClinVar RCV000239244, REVEL 0.37, CADD 21.60, Likely benign, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- P65H (p.Pro65His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P65S (p.Pro65Ser), Ensembl rs2094245870
- P65T (p.Pro65Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V66M (p.Val66Met), TOPMed rs992942163, REVEL 0.34, CADD 26.00
- Y67S (p.Tyr67Ser), Ensembl rs2147700150
- H68Y (p.His68Tyr), Ensembl rs2147700145
- S69F (p.Ser69Phe), ExAC rs747943549, gnomAD rs747943549, REVEL 0.34, CADD 24.20
- L70V (p.Leu70Val), cosmic curated COSV71686, ExAC rs770063056, gnomAD rs770063056, REVEL 0.61, CADD 25.60
- L73R (p.Leu73Arg), rs1064793156, ClinGen CA16620809, ClinVar RCV000481431, TOPMed rs1064793156, REVEL 0.83, CADD 29.00, Conflicting interpretations, not provided; not specified
- L73V (p.Leu73Val), rs2094245829, ClinGen CA404774678, ClinVar RCV001977633, TOPMed rs2094245829, REVEL 0.48, CADD 22.90, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- A74V (p.Ala74Val), Ensembl rs2147700122, REVEL 0.23, CADD 23.80
- T75M (p.Thr75Met), cosmic curated COSV10151, ExAC rs745933382, gnomAD rs745933382, REVEL 0.38, CADD 21.10
- E76G (p.Glu76Gly), Ensembl rs2147700109
- E76K (p.Glu76Lys), NCI-TCGA Cosmic COSV7168, cosmic curated COSV71686, Variant assessed as somatic; moderate impact.
- D77A (p.Asp77Ala), Ensembl rs2147700101
- D77V (p.Asp77Val), cosmic curated COSV10753, Ensembl rs2147700101
- D77Y (p.Asp77Tyr), TOPMed rs1350333034
- C80Y (p.Cys80Tyr), Ensembl rs2147700080
- W81C (p.Trp81Cys), rs2094245783, ClinGen CA2326057806, ClinVar RCV003510188, Pathogenic
- W81L (p.Trp81Leu), cosmic curated COSV71685
- F82I (p.Phe82Ile), TOPMed rs1323877308, gnomAD rs1323877308, REVEL 0.47, CADD 25.20
- F82L (p.Phe82Leu), cosmic curated COSV71685
- F82S (p.Phe82Ser), cosmic curated COSV10895, ExAC rs201587905, gnomAD rs201587905, REVEL 0.53, CADD 25.30
- F82Y (p.Phe82Tyr), ExAC rs201587905, gnomAD rs201587905
- P83L (p.Pro83Leu), cosmic curated COSV10974
- P83S (p.Pro83Ser), NCI-TCGA Cosmic COSV7168, cosmic curated COSV71686, REVEL 0.35, CADD 23.60, Variant assessed as somatic; moderate impact.
- P83T (p.Pro83Thr), Ensembl rs2147700059
- P84A (p.Pro84Ala), gnomAD rs1236673227, REVEL 0.73, CADD 25.00
- P84L (p.Pro84Leu), rs201067961, ClinGen CA9302215, cosmic curated COSV10594, ClinVar RCV002581641, REVEL 0.67, CADD 26.20, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- P84R (p.Pro84Arg), cosmic curated COSV10974, ExAC rs201067961, TOPMed rs201067961, gnomAD rs201067961, REVEL 0.73, CADD 26.30, Uncertain significance
- P84S (p.Pro84Ser), gnomAD rs1236673227
- S85C (p.Ser85Cys), Ensembl rs2147700029
- S85N (p.Ser85Asn), TOPMed rs1299325240, REVEL 0.15, CADD 13.70
- S85R (p.Ser85Arg), Ensembl rs2147700029, REVEL 0.41, CADD 22.80
- I87T (p.Ile87Thr), cosmic curated COSV71686, Ensembl rs1057519770
- I87V (p.Ile87Val), cosmic curated COSV71687
- V90M (p.Val90Met), rs1016346013, ClinGen CA306141734, ClinVar RCV002266247, ClinVar RCV003096014, REVEL 0.12, CADD 16.40, Uncertain significance, Inborn genetic diseases; T-B+ severe combined immunodeficiency due to JAK3 defic
- E91G (p.Glu91Gly), Ensembl rs2147699997
- D92H (p.Asp92His), TOPMed rs1323968278
- D92N (p.Asp92Asn), rs1323968278, TOPMed rs1323968278, AlphaMissense 0.22, MetaLR 0.50, Variant assessed as somatic; moderate impact.
- A93T (p.Ala93Thr), TOPMed rs1219986698, gnomAD rs1219986698, REVEL 0.18, CADD 3.16
- A93V (p.Ala93Val), cosmic curated COSV10753, Ensembl rs2147699988
- S94N (p.Ser94Asn), rs2147699985, ClinGen CA404774451, ClinVar RCV003051774, Ensembl rs2147699985, AlphaMissense 0.07, MetaLR 0.19, Uncertain significance, T-B+ severe combined immunodeficiency due to JAK3 deficiency
- Q96E (p.Gln96Glu), TOPMed rs2094245638, gnomAD rs2094245638, REVEL 0.12, CADD 14.20
Public JAK3 analysis runs
- JAK3 analysis run — JAK3 (2,778 variants) — completed 2026-08-19