IL2RG (P31785) variants and mutations
IL2RG (also known as P31785) is a human protein-coding gene encoding a cytokine receptor common subunit gamma protein. It is the shared signaling chain used by receptors for several interleukins required for lymphocyte development and survival. Loss-of-function variants cause X-linked severe combined immunodeficiency with profound T-cell and natural-killer-cell deficiency. This analysis covers 591 IL2RG variants and mutations. Of these, 76% have computational variant effect predictions. Disease context includes T-B+ severe combined immunodeficiency due to gamma chain deficiency, combined immunodeficiency, X-linked, and Omenn syndrome. Example IL2RG variants include M1T, K3N, and K3*.
Variant analysis overview
- Gene: IL2RG
- Protein: P31785
- UniProt accession: P31785
- Organism: Homo sapiens
- Variants analyzed: 591
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 377 unspecified-consequence records; 2 stop lost; 72 synonymous variants; 123 missense variants; 8 frameshift variants; 4 stop-gained variants; 5 splice-region variants; 2 substitution
- Prediction scores: 452 variants have prediction scores (76% 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 gamma chain deficiency, combined immunodeficiency, X-linked, Omenn syndrome, primary cutaneous T-cell non-Hodgkin lymphoma, renal cell carcinoma, multiple sclerosis, kidney transplant, neoplasm, metastatic melanoma, immune system disorder, severe combined immunodeficiency, T-B- severe combined immunodeficiency.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 7 post-translational modification sites.
- Structural context: 214 variants have structural context.
- PTM context: 3 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 IL2RG variants
Examples include M1T, K3N, K3*, P4L, L6S, T9I, L11F, L11H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1T (p.Met1Thr), rs886041334, ClinGen CA10603689, ClinVar RCV000301048, ClinVar RCV006462295, MetaLR 0.70, MetaSVM 0.39, Pathogenic, X-linked severe combined immunodeficiency; not provided
- K3N (p.Lys3Asn), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- K3* (p.Lys3Ter), rs2147748094, gnomAD X-71109232-T-A, CADD 7.17
- P4L (p.Pro4Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L6S (p.Leu6Ser), rs2092264087, ClinGen CA413497767, ClinVar RCV001911807, TOPMed rs2092264087, REVEL 0.19, CADD 14.60, Uncertain significance, X-linked severe combined immunodeficiency; Inborn genetic diseases
- T9I (p.Thr9Ile), TOPMed rs950882646, gnomAD rs950882646, REVEL 0.24, CADD 12.40, Uncertain significance, X-linked severe combined immunodeficiency
- L11F (p.Leu11Phe), rs1394628494, ClinGen CA413497738, ClinVar RCV002299717, gnomAD rs1394628494, REVEL 0.14, CADD 0.41, Uncertain significance, X-linked severe combined immunodeficiency
- L11H (p.Leu11His), TOPMed rs1204738180, gnomAD rs1204738180, REVEL 0.50, AlphaMissense 0.21, Uncertain significance
- L11P (p.Leu11Pro), rs1204738180, ClinGen CA413497734, ClinVar RCV002005549, TOPMed rs1204738180, AlphaMissense 0.21, MetaLR 0.83, Uncertain significance, X-linked severe combined immunodeficiency
- F13L (p.Phe13Leu), rs1015272346, ClinGen CA330970891, ClinVar RCV001050625, ClinVar RCV002553227, REVEL 0.34, CADD 8.92, Conflicting interpretations, IL2RG-related disorder; X-linked severe combined immunodeficiency; Inborn geneti
- L14P (p.Leu14Pro), rs2519648777, ClinGen CA413497716, ClinVar RCV002284056, Likely pathogenic, X-linked severe combined immunodeficiency
- Q15* (p.Gln15Ter), rs1057517747, ClinGen CA16043285, ClinVar RCV000412822, ClinVar RCV001251321, Pathogenic
- L16P (p.Leu16Pro), rs879253742, ClinGen CA10584017, ClinVar RCV000234914, Ensembl rs879253742, AlphaMissense 0.34, MetaLR 0.90, Likely pathogenic
- L18P (p.Leu18Pro), NCI-TCGA Cosmic COSV5215, Variant assessed as somatic; moderate impact.
- G20A (p.Gly20Ala), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- G20E (p.Gly20Glu), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- V21A (p.Val21Ala), rs376612175, ClinGen CA330970880, ClinVar RCV001057331, Ensembl rs376612175, AlphaMissense 0.09, MetaLR 0.66, Uncertain significance, X-linked severe combined immunodeficiency
- V21L (p.Val21Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T25M (p.Thr25Met), rs751455361, ClinGen CA10443955, ClinVar RCV002095920, ClinVar RCV005854214, REVEL 0.32, CADD 17.40, Conflicting interpretations, Inborn genetic diseases; X-linked severe combined immunodeficiency
- I27N (p.Ile27Asn), rs2519648692, ClinGen CA2580101353, ClinVar RCV003057666, REVEL 0.24, CADD 14.00, Pathogenic
- I27T (p.Ile27Thr), rs2519648690, ClinGen CA413497641, ClinVar RCV003510102, Uncertain significance, X-linked severe combined immunodeficiency
- L28V (p.Leu28Val), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- T29M (p.Thr29Met), rs375921454, ClinGen CA10443951, ClinVar RCV000924456, ClinVar RCV004029499, REVEL 0.18, CADD 5.40, Conflicting interpretations, Inborn genetic diseases; X-linked severe combined immunodeficiency
- P30T (p.Pro30Thr), ExAC rs755952194, gnomAD rs755952194, REVEL 0.27, CADD 15.30
- N31I (p.Asn31Ile), rs749977756, ClinGen CA413497619, ClinVar RCV003081644, ExAC rs749977756, MetaLR 0.55, MetaSVM -0.41, Benign, X-linked severe combined immunodeficiency
- N31S (p.Asn31Ser), rs749977756, ClinGen CA10443948, ClinVar RCV000922028, ExAC rs749977756, MetaLR 0.55, MetaSVM -0.41, Benign, X-linked severe combined immunodeficiency
- G32V (p.Gly32Val), NCI-TCGA Cosmic COSV5214, cosmic curated COSV52148, Variant assessed as somatic; moderate impact.
- N33D (p.Asn33Asp), rs2519648648, ClinGen CA413497605, ClinVar RCV002580618, REVEL 0.39, CADD 25.20, Uncertain significance, X-linked severe combined immunodeficiency
- N33S (p.Asn33Ser), rs2519648645, ClinGen CA413497603, ClinVar RCV003131264, Uncertain significance, not provided
- E34* (p.Glu34Ter), rs1556331272, ClinGen CA413497595, NCI-TCGA Cosmic COSV5214, cosmic curated COSV52147, Pathogenic
- E34K (p.Glu34Lys), rs2147748101, gnomAD X-71109244-C-T, CADD 4.13
- D35H (p.Asp35His), cosmic curated COSV10959, Ensembl rs2092263840, REVEL 0.72, CADD 32.00
- D39G (p.Asp39Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in XSCID
- D39N (p.Asp39Asn), UniProt VAR 002668, Pathogenic, in XSCID
- F41L (p.Phe41Leu), TOPMed rs1160105152, REVEL 0.28, CADD 15.60
- T44A (p.Thr44Ala), rs7885041, ClinGen CA10443921, ClinVar RCV001468819, ClinVar RCV003130523, REVEL 0.22, CADD 10.20, Conflicting interpretations, not provided; X-linked severe combined immunodeficiency
- T44S (p.Thr44Ser), rs7885041, UniProt VAR 059301, ExAC rs7885041, TOPMed rs7885041, REVEL 0.28, CADD 7.52, Likely benign
- M45I (p.Met45Ile), TOPMed rs1376812775, gnomAD rs1376812775
- M45L (p.Met45Leu), TOPMed rs1173646768
- M45V (p.Met45Val), TOPMed rs1173646768
- S49F (p.Ser49Phe), gnomAD rs1248436662, REVEL 0.26, CADD 15.00
- S51R (p.Ser51Arg), rs2519648029, ClinGen CA413497226, ClinVar RCV003623528, REVEL 0.22, CADD 7.45, Uncertain significance, X-linked severe combined immunodeficiency
- V52A (p.Val52Ala), ExAC rs767725593, gnomAD rs767725593, REVEL 0.23, CADD 8.36
- T54I (p.Thr54Ile), gnomAD rs1256746654, REVEL 0.20, CADD 12.00
- P56L (p.Pro56Leu), rs774569887, ClinGen CA10443916, ClinVar RCV000386941, ExAC rs774569887, REVEL 0.60, CADD 23.90, Uncertain significance, X-linked severe combined immunodeficiency
- P56R (p.Pro56Arg), ExAC rs774569887, TOPMed rs774569887, gnomAD rs774569887, REVEL 0.60, CADD 24.00, Uncertain significance
- P56S (p.Pro56Ser), TOPMed rs1336706562, gnomAD rs1336706562, REVEL 0.39, CADD 22.80
- P58T (p.Pro58Thr), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- P58L (p.Pro58Leu), gnomAD X-71108325-G-A, CADD 10.40
- P58H (p.Pro58His), rs2092255514, gnomAD X-71108337-G-T, CADD 10.50
- E59* (p.Glu59Ter), rs2092262517, ClinGen CA413497183, ClinVar RCV002222990, Ensembl rs2092262517, AlphaMissense 0.07, MetaLR 0.24, Likely pathogenic
- E59K (p.Glu59Lys), Ensembl rs2092262517, REVEL 0.21, AlphaMissense 0.07, Likely pathogenic
- V60F (p.Val60Phe), Ensembl rs2147750995, REVEL 0.68, CADD 24.70
- Q61* (p.Gln61Ter), rs1569480082, ClinGen CA413497169, ClinVar RCV000781479, Ensembl rs1569480082, Likely pathogenic
- Q61H (p.Gln61His), TOPMed rs1353533514
- C62* (p.Cys62Ter), rs111033619, ClinGen CA254980, ClinVar RCV000010702, Ensembl rs111033619, Pathogenic, in XSCID
- C62G (p.Cys62Gly), UniProt VAR 002669, Pathogenic, in XSCID
- C62R (p.Cys62Arg), rs1602289649, ClinGen CA413497163, ClinVar RCV001377072, ClinVar RCV001751746, AlphaMissense 0.99, MetaLR 0.95, Pathogenic, X-linked severe combined immunodeficiency
- C62S (p.Cys62Ser), rs1602289649, ClinGen CA413497161, ClinVar RCV000788884, ClinVar RCV004765338, AlphaMissense 0.99, MetaLR 0.95, Likely pathogenic, X-linked severe combined immunodeficiency
- V64M (p.Val64Met), rs1131691781, ClinGen CA413497146, ClinVar RCV000494129, Ensembl rs1131691781, AlphaMissense 0.72, MetaLR 0.90, Uncertain significance, not provided
- F65L (p.Phe65Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V67I (p.Val67Ile), ExAC rs775243259, gnomAD rs775243259, REVEL 0.21, CADD 13.00
- E68G (p.Glu68Gly), UniProt VAR 002670, Pathogenic, in XSCID
- E68K (p.Glu68Lys), rs1057520644, ClinGen CA16608976, ClinVar RCV000427716, ClinVar RCV000638843, AlphaMissense 0.33, MetaLR 0.87, Pathogenic, X-linked severe combined immunodeficiency
- Y69* (p.Tyr69Ter), rs1282558220, ClinGen CA413497107, ClinVar RCV001211090, TOPMed rs1282558220, Pathogenic
- Y69C (p.Tyr69Cys), rs2519647963, ClinGen CA413497109, ClinVar RCV003022542, Conflicting interpretations, X-linked severe combined immunodeficiency
- N71T (p.Asn71Thr), rs1556330963, ClinGen CA645373305, ClinVar RCV000498292, Ensembl rs1556330963, Pathogenic
- C72* (p.Cys72Ter), rs2147750927, ClinGen CA413497082, ClinVar RCV001899190, Ensembl rs2147750927, Likely pathogenic
- C72F (p.Cys72Phe), rs1556330960, ClinGen CA413497083, ClinVar RCV000524824, Ensembl rs1556330960, AlphaMissense 0.95, MetaLR 0.96, Uncertain significance, X-linked severe combined immunodeficiency
- S76G (p.Ser76Gly), rs745652226, ClinGen CA10443911, ClinVar RCV001245376, ExAC rs745652226, REVEL 0.48, CADD 23.10, Uncertain significance, X-linked severe combined immunodeficiency
- S77R (p.Ser77Arg), Ensembl rs1556330951, REVEL 0.55, CADD 23.40, Likely benign
- S78P (p.Ser78Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E79C (p.Glu79Cys), rs2519647922, ClinGen CA2580101348, ClinVar RCV002309026, Likely pathogenic
- P80H (p.Pro80His), TOPMed rs1343008020, gnomAD rs1343008020, REVEL 0.46, CADD 23.90
- P80L (p.Pro80Leu), rs1343008020, ClinGen CA413497023, ClinVar RCV003133702, ClinVar RCV005099299, REVEL 0.21, CADD 19.90, Uncertain significance, X-linked severe combined immunodeficiency; not provided
- P80T (p.Pro80Thr), rs2147750896, ClinGen CA413497028, ClinVar RCV001915015, Ensembl rs2147750896, AlphaMissense 0.09, MetaLR 0.76, Uncertain significance, X-linked severe combined immunodeficiency
- Q81H (p.Gln81His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T83S (p.Thr83Ser), NCI-TCGA Cosmic COSV9934, Variant assessed as somatic; moderate impact.
- N84K (p.Asn84Lys), rs1356632210, ClinGen CA413496996, ClinVar RCV001758148, UniProt VAR 002672, AlphaMissense 0.77, MetaLR 0.90, Uncertain significance, not provided
- L87M (p.Leu87Met), gnomAD rs1312845538
- L87P (p.Leu87Pro), rs1057520293, ClinGen CA16608908, ClinVar RCV000426062, Ensembl rs1057520293, AlphaMissense 0.96, MetaLR 0.88, Likely pathogenic, not provided
- Y89C (p.Tyr89Cys), rs2519647897, ClinGen CA413496966, ClinVar RCV003509058, UniProt VAR 002673, Uncertain significance, X-linked severe combined immunodeficiency
- Y89F (p.Tyr89Phe), NCI-TCGA Cosmic COSV5215, Variant assessed as somatic; moderate impact., in XSCID
- W90* (p.Trp90Ter), rs1569480047, ClinGen CA413496944, ClinVar RCV000690121, Ensembl rs1569480047, AlphaMissense 0.73, MetaLR 0.74, Pathogenic
- W90C (p.Trp90Cys), rs1569480047, ClinGen CA413496943, ClinVar RCV002607397, ClinGen CA413496942, AlphaMissense 0.73, MetaLR 0.74, Uncertain significance, X-linked severe combined immunodeficiency
- W90L (p.Trp90Leu), rs2092262308, ClinGen CA413496957, NCI-TCGA Cosmic COSV9934, ClinVar RCV001238084, AlphaMissense 0.25, MetaLR 0.68, Uncertain significance, X-linked severe combined immunodeficiency
- Y91C (p.Tyr91Cys), gnomAD rs1293196743, REVEL 0.73, CADD 25.10
- K92N (p.Lys92Asn), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- K92R (p.Lys92Arg), gnomAD rs2092261715, REVEL 0.29, CADD 11.10
- N93S (p.Asn93Ser), rs2519647443, ClinGen CA413496921, ClinVar RCV002298116, Uncertain significance, X-linked severe combined immunodeficiency
- S94* (p.Ser94Ter), rs775704953, ClinGen CA413496915, ClinVar RCV000579336, ClinVar RCV003509571, AlphaMissense 0.11, MetaLR 0.68, Pathogenic
- S94L (p.Ser94Leu), rs775704953, ClinGen CA10443894, ClinVar RCV000941304, ClinVar RCV003372919, REVEL 0.31, AlphaMissense 0.11, Conflicting interpretations, Inborn genetic diseases; X-linked severe combined immunodeficiency
- S94T (p.Ser94Thr), rs201187311, ClinGen CA10443895, ClinVar RCV001923706, ESP rs201187311, REVEL 0.27, CADD 8.67, Uncertain significance, X-linked severe combined immunodeficiency
- D97Y (p.Asp97Tyr), TOPMed rs2092261643, REVEL 0.46, CADD 12.00, Uncertain significance, X-linked severe combined immunodeficiency
- K98E (p.Lys98Glu), rs776710796, ClinGen CA10443891, ClinVar RCV000990860, ExAC rs776710796, REVEL 0.55, CADD 9.15, Uncertain significance, X-linked severe combined immunodeficiency
- S103C (p.Ser103Cys), Ensembl rs112272299
- S103N (p.Ser103Asn), TOPMed rs2092261574, REVEL 0.27, CADD 19.30
- S103R (p.Ser103Arg), Ensembl rs112272299, REVEL 0.38, CADD 16.70
- H104L (p.His104Leu), rs770804846, ClinGen CA10443890, ClinVar RCV001240284, ExAC rs770804846, REVEL 0.67, CADD 22.70, Likely benign, X-linked severe combined immunodeficiency
- Y105C (p.Tyr105Cys), rs193922347, ClinGen CA260411, ClinVar RCV000030054, UniProt VAR 002674, AlphaMissense 0.92, MetaLR 0.92, Pathogenic, in XSCID
- L106I (p.Leu106Ile), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- E109* (p.Glu109Ter), 1000Genomes rs17875899, ESP rs17875899, ExAC rs17875899, TOPMed rs17875899, Benign
- E109G (p.Glu109Gly), Ensembl rs2147750393, REVEL 0.24, CADD 11.50
- E109K (p.Glu109Lys), rs17875899, ClinGen CA10443889, ClinVar RCV000610972, ClinVar RCV000638846, REVEL 0.28, CADD 10.30, Benign, X-linked severe combined immunodeficiency
- E109Q (p.Glu109Gln), 1000Genomes rs17875899, ESP rs17875899, ExAC rs17875899, TOPMed rs17875899, Benign
- E110* (p.Glu110Ter), rs2147750382, ClinGen CA413496806, ClinVar RCV001878969, Ensembl rs2147750382, Pathogenic
- I111M (p.Ile111Met), rs1373609177, ClinGen CA413496795, ClinVar RCV002218710, gnomAD rs1373609177, REVEL 0.42, CADD 17.90, Likely benign, X-linked severe combined immunodeficiency
- I111T (p.Ile111Thr), rs778229878, ClinGen CA10443887, ClinVar RCV000978621, 1000Genomes rs778229878, REVEL 0.40, CADD 14.70, Likely benign, X-linked severe combined immunodeficiency
- I111V (p.Ile111Val), TOPMed rs2092261466, gnomAD rs2092261466, REVEL 0.14, CADD 4.48
- S113Y (p.Ser113Tyr), NCI-TCGA Cosmic COSV9934, Variant assessed as somatic; moderate impact.
- G114C (p.Gly114Cys), rs2147750359, ClinGen CA413496780, ClinVar RCV001378640, Ensembl rs2147750359, AlphaMissense 0.93, MetaLR 0.92, Pathogenic, X-linked severe combined immunodeficiency
- G114D (p.Gly114Asp), rs111033620, ClinGen CA254983, ClinVar RCV000010703, UniProt VAR 002675, AlphaMissense 0.95, MetaLR 0.92, Pathogenic, in XSCID
- G114S (p.Gly114Ser), rs2147750359, ClinGen CA413496782, ClinVar RCV003150601, AlphaMissense 0.93, MetaLR 0.92, Likely pathogenic, X-linked severe combined immunodeficiency
- C115F (p.Cys115Phe), rs1556330755, ClinGen CA413496773, ClinVar RCV001969652, UniProt VAR 002676, AlphaMissense 0.96, MetaLR 1.00, Likely pathogenic, X-linked severe combined immunodeficiency
- C115R (p.Cys115Arg), rs111033622, ClinGen CA254990, ClinVar RCV000010708, UniProt VAR 002677, AlphaMissense 0.98, MetaLR 1.00, Pathogenic, in XSCID
- C115Y (p.Cys115Tyr), rs1556330755, ClinGen CA413496775, ClinVar RCV000554205, Ensembl rs1556330755, AlphaMissense 0.96, MetaLR 1.00, Likely pathogenic, X-linked severe combined immunodeficiency
- Q116H (p.Gln116His), rs778547446, ClinGen CA10443885, ClinVar RCV001517355, ExAC rs778547446, REVEL 0.19, CADD 15.90, Likely benign, X-linked severe combined immunodeficiency
- Q116P (p.Gln116Pro), rs1556330752, ClinGen CA413496765, ClinVar RCV000523698, Ensembl rs1556330752, AlphaMissense 0.49, MetaLR 0.75, Uncertain significance, not provided
- Q118* (p.Gln118Ter), rs2519647207, ClinGen CA413496754, ClinVar RCV003509057, Pathogenic
- Q118A (p.Gln118Ala), rs2519647217, ClinGen CA2697553151, ClinVar RCV003510264, Pathogenic
- Q118P (p.Gln118Pro), gnomAD rs1193935875, REVEL 0.51, CADD 1.76
- K119* (p.Lys119Ter), rs137852507, ClinGen CA254974, ClinVar RCV000010699, ExAC rs137852507, AlphaMissense 0.12, MetaLR 0.74, Pathogenic
- K119Q (p.Lys119Gln), ExAC rs137852507, gnomAD rs137852507, REVEL 0.16, AlphaMissense 0.12, Pathogenic
- K120E (p.Lys120Glu), rs2519647190, ClinGen CA413496742, ClinVar RCV003622906, REVEL 0.30, CADD 5.01, Uncertain significance, X-linked severe combined immunodeficiency
- K120N (p.Lys120Asn), gnomAD rs1270657479, REVEL 0.10, CADD 5.57
- K120R (p.Lys120Arg), TOPMed rs1277860701
- I122N (p.Ile122Asn), rs2147750291, ClinGen CA413496721, ClinVar RCV001816542, Ensembl rs2147750291, AlphaMissense 0.64, MetaLR 0.90, Likely pathogenic, not provided
- H123P (p.His123Pro), UniProt VAR 002678, Pathogenic, in XSCID
- Y125C (p.Tyr125Cys), rs2092261313, ClinGen CA413496701, ClinVar RCV001280968, Ensembl rs2092261313, AlphaMissense 0.87, MetaLR 0.87, Likely pathogenic, Combined immunodeficiency, X-linked; X-linked severe combined immunodeficiency
- Y125N (p.Tyr125Asn), UniProt VAR 002679, Pathogenic, in XSCID
- Q126H (p.Gln126His), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- V130L (p.Val130Leu), gnomAD rs1342024883, REVEL 0.42, CADD 19.40
- Q131* (p.Gln131Ter), rs1131691652, ClinGen CA413496661, ClinVar RCV000493602, Ensembl rs1131691652, Pathogenic
- L132H (p.Leu132His), rs2092261278, ClinGen CA413496652, ClinVar RCV002026875, ClinVar RCV003491018, AlphaMissense 0.69, MetaLR 0.70, Conflicting interpretations, not specified; X-linked severe combined immunodeficiency
- L132R (p.Leu132Arg), rs2092261278, ClinGen CA413496650, ClinVar RCV001348095, Ensembl rs2092261278, AlphaMissense 0.69, MetaLR 0.70, Uncertain significance, X-linked severe combined immunodeficiency
- D134G (p.Asp134Gly), rs2147750229, ClinGen CA413496637, ClinVar RCV001944491, Ensembl rs2147750229, AlphaMissense 0.74, MetaLR 0.48, Uncertain significance, X-linked severe combined immunodeficiency
- R136Q (p.Arg136Gln), rs753502444, ClinGen CA10443881, ClinVar RCV001521032, 1000Genomes rs753502444, REVEL 0.06, CADD 8.59, Benign, X-linked severe combined immunodeficiency
- R136W (p.Arg136Trp), rs758080286, ClinGen CA330970071, ClinVar RCV000638844, TOPMed rs758080286, REVEL 0.45, CADD 22.90, Likely benign, X-linked severe combined immunodeficiency
- E137* (p.Glu137Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P138S (p.Pro138Ser), rs1266997803, ClinGen CA413496614, ClinVar RCV001875385, TOPMed rs1266997803, REVEL 0.18, CADD 13.50, Uncertain significance, X-linked severe combined immunodeficiency
- R139K (p.Arg139Lys), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- R140K (p.Arg140Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R140T (p.Arg140Thr), rs2147750206, ClinGen CA413496599, ClinVar RCV001531161, Ensembl rs2147750206, AlphaMissense 0.40, MetaLR 0.86, Uncertain significance, not provided
- Q141* (p.Gln141Ter), rs1556330713, ClinGen CA413496594, ClinVar RCV000519478, ClinVar RCV000990859, Pathogenic
- A142T (p.Ala142Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q144* (p.Gln144Ter), rs1602289411, ClinGen CA413496574, ClinVar RCV000804431, Ensembl rs1602289411, Pathogenic, in XSCID
- Q144H (p.Gln144His), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact., in XSCID
- Q144P (p.Gln144Pro), UniProt VAR 002680, Pathogenic, in XSCID
- Q144R (p.Gln144Arg), TOPMed rs752240137, gnomAD rs752240137, REVEL 0.31, CADD 13.50, Uncertain significance, Inborn genetic diseases
- M145K (p.Met145Lys), rs751970923, ClinGen CA10443880, ClinVar RCV001401617, ClinVar RCV003898409, REVEL 0.37, CADD 0.06, Likely benign, Inborn genetic diseases; X-linked severe combined immunodeficiency
- M145V (p.Met145Val), rs1602289401, ClinGen CA413496568, ClinVar RCV000812128, Ensembl rs1602289401, AlphaMissense 0.10, MetaLR 0.72, Uncertain significance, X-linked severe combined immunodeficiency
- L146P (p.Leu146Pro), rs2519647063, ClinGen CA413496558, ClinVar RCV003041455, Likely pathogenic, X-linked severe combined immunodeficiency
- N150H (p.Asn150His), NCI-TCGA Cosmic COSV5215, Variant assessed as somatic; moderate impact.
- L151P (p.Leu151Pro), rs137852511, ClinGen CA254994, ClinVar RCV000010711, Ensembl rs137852511, AlphaMissense 0.95, MetaLR 0.87, Uncertain significance
- V152A (p.Val152Ala), rs193922348, ClinGen CA260413, ClinVar RCV000030055, Ensembl rs193922348, AlphaMissense 0.71, MetaLR 0.92, Pathogenic
- V152G (p.Val152Gly), rs193922348, ClinGen CA413496508, ClinVar RCV000766121, Ensembl rs193922348, AlphaMissense 0.71, MetaLR 0.92, Likely pathogenic, X-linked severe combined immunodeficiency
- I153N (p.Ile153Asn), rs111033621, ClinGen CA254985, ClinVar RCV000010705, UniProt VAR 002681, AlphaMissense 0.83, MetaLR 0.82, Pathogenic, in XSCID
- I153T (p.Ile153Thr), rs111033621, ClinGen CA413496503, ClinVar RCV001090305, Ensembl rs111033621, AlphaMissense 0.83, MetaLR 0.82, Likely pathogenic, not provided
- I153I (p.Ile153Ile), rs150560580, gnomAD X-71110291-G-A, CADD 9.33
- P154H (p.Pro154His), rs1602289242, ClinGen CA413496497, ClinVar RCV000803412, Ensembl rs1602289242, AlphaMissense 0.96, MetaLR 0.99, Uncertain significance, X-linked severe combined immunodeficiency
- P154S (p.Pro154Ser), rs1064793153, ClinGen CA16621485, ClinVar RCV000480139, ClinVar RCV002525762, AlphaMissense 0.91, MetaLR 0.99, Uncertain significance, X-linked severe combined immunodeficiency
- W155* (p.Trp155Ter), rs1569479994, ClinGen CA413496489, ClinVar RCV000781480, Ensembl rs1569479994, Likely pathogenic
- W155R (p.Trp155Arg), rs2147749841, ClinGen CA413496495, ClinVar RCV001867493, ClinVar RCV005861255, AlphaMissense 0.36, MetaLR 0.61, Uncertain significance, not provided; X-linked severe combined immunodeficiency
- W155S (p.Trp155Ser), rs1485784611, ClinGen CA413496491, ClinVar RCV003043316, Ensembl rs1485784611, AlphaMissense 0.17, MetaLR 0.53, Uncertain significance, X-linked severe combined immunodeficiency
- A156V (p.Ala156Val), rs1057521062, ClinGen CA16608907, ClinVar RCV000435698, ClinVar RCV001235346, AlphaMissense 0.49, MetaLR 0.89, Likely pathogenic, not provided; X-linked severe combined immunodeficiency
- A156T (p.Ala156Thr), gnomAD X-71110284-C-T, REVEL 0.81, CADD 24.50
- L162H (p.Leu162His), UniProt VAR 002683, Pathogenic, in XSCID
- L162R (p.Leu162Arg), rs2092260648, ClinGen CA413496443, ClinVar RCV001236375, Ensembl rs2092260648, AlphaMissense 0.66, MetaLR 0.91, Likely pathogenic, X-linked severe combined immunodeficiency
- L162V (p.Leu162Val), rs2147749821, ClinGen CA413496448, ClinVar RCV001733815, ClinVar RCV002032743, AlphaMissense 0.11, MetaLR 0.66, Uncertain significance, not specified; Combined immunodeficiency, X-linked; X-linked severe combined imm
- H163D (p.His163Asp), TOPMed rs1020615876
- H163R (p.His163Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K164I (p.Lys164Ile), rs1009255987, ClinGen CA413496431, ClinVar RCV003030559, AlphaMissense 0.07, MetaLR 0.57, Uncertain significance, X-linked severe combined immunodeficiency
- K164R (p.Lys164Arg), TOPMed rs1009255987, gnomAD rs1009255987, REVEL 0.08, AlphaMissense 0.07
- L165R (p.Leu165Arg), rs758693125, ClinGen CA10443860, ClinVar RCV000941522, ClinVar RCV003438607, REVEL 0.32, CADD 18.90, Conflicting interpretations, not provided; Inborn genetic diseases; X-linked severe combined immunodeficiency
- L165L (p.Leu165Leu), rs778140826, gnomAD X-71110257-G-A, CADD 8.24
- S166R (p.Ser166Arg), 1000Genomes rs199593676, TOPMed rs199593676, gnomAD rs199593676, REVEL 0.42, CADD 20.70
- S166S (p.Ser166Ser), rs199593676, gnomAD X-71110252-A-G, CADD 6.92
- E167D (p.Glu167Asp), NCI-TCGA Cosmic COSV5214, Variant assessed as somatic; moderate impact.
- S168F (p.Ser168Phe), TOPMed rs1382662571, gnomAD rs1382662571, REVEL 0.27, CADD 18.60
- S168S (p.Ser168Ser), rs752921124, gnomAD X-71110246-G-A, CADD 10.10
Public IL2RG analysis runs
- IL2RG analysis run — IL2RG (591 variants) — completed 2026-08-21