CTLA4 (Cytotoxic T-lymphocyte protein 4) variants and mutations
CTLA4 (also known as Cytotoxic T-lymphocyte protein 4) is a human protein-coding gene encoding a cytotoxic T-lymphocyte protein 4 protein. It restrains T-cell activation by competing with CD28 for CD80 and CD86 and by delivering inhibitory signals after immune activation. Haploinsufficiency causes immune dysregulation with autoimmunity and lymphoproliferation, while therapeutic blockade enhances antitumor immunity. This analysis covers 474 CTLA4 variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency, Hashimoto thyroiditis, and systemic lupus erythematosus. Example CTLA4 variants include A2S, A2V, and A2T.
Variant analysis overview
- Gene: CTLA4
- Protein: Cytotoxic T-lymphocyte protein 4
- UniProt accession: P16410
- Organism: Homo sapiens
- Variants analyzed: 474
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 287 unspecified-consequence records; 86 missense variants; 90 synonymous variants; 5 frameshift variants; 4 splice-region variants; 1 stop-gained variants; 1 stop lost
- Prediction scores: 364 variants have prediction scores (77% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency, Hashimoto thyroiditis, systemic lupus erythematosus, melanoma, non-small cell lung carcinoma, hepatocellular carcinoma, rheumatoid arthritis, hypothyroidism, type 1 diabetes mellitus, Graves disease, renal cell carcinoma, thyroid gland disorder.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 3 post-translational modification sites.
- Structural context: 272 variants have structural context.
- PTM context: 6 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 CTLA4 variants
Examples include A2S, A2V, A2T, C3F, C3R, L4F, L4L, F6I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2S (p.Ala2Ser), rs767352102, ClinGen CA2067028, ClinVar RCV000652448, ExAC rs767352102, MetaLR 0.12, MetaSVM -0.97, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- A2V (p.Ala2Val), TOPMed rs1688656832
- A2T (p.Ala2Thr), gnomAD 2-203867946-G-A, MetaLR 0.10, MetaSVM -1.03
- C3F (p.Cys3Phe), TOPMed rs1289408071, gnomAD rs1289408071, MetaLR 0.07, MetaSVM -1.06, Likely benign, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- C3R (p.Cys3Arg), gnomAD 2-203867949-T-C, MetaLR 0.04, MetaSVM -1.02
- L4F (p.Leu4Phe), Ensembl rs1688656933, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- L4L (p.Leu4Leu), rs1688656987, gnomAD 2-203867954-T-G, CADD 8.48
- F6I (p.Phe6Ile), Ensembl rs896306346
- Q7* (p.Gln7Ter), NCI-TCGA Cosmic COSV9986, cosmic curated COSV99865, Variant assessed as somatic; high impact.
- R8L (p.Arg8Leu), rs138279736, ClinGen CA2067030, cosmic curated COSV99865, ClinVar RCV002592440, MetaLR 0.10, MetaSVM -1.02, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- R8Q (p.Arg8Gln), rs138279736, ClinGen CA2067031, ClinVar RCV000545159, 1000Genomes rs138279736, MetaLR 0.08, MetaSVM -1.05, Benign, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- R8W (p.Arg8Trp), rs201778935, ClinGen CA2067029, cosmic curated COSV55592, ClinVar RCV001299100, MetaLR 0.13, MetaSVM -1.02, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- R8R (p.Arg8Arg), gnomAD 2-203867964-C-A, CADD 3.56
- H9H (p.His9His), rs1688657403, gnomAD 2-203867969-C-T, CADD 0.29
- K10E (p.Lys10Glu), ESP rs146541851, ExAC rs146541851, TOPMed rs146541851, gnomAD rs146541851, MetaLR 0.05, MetaSVM -1.02
- K10T (p.Lys10Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K10K (p.Lys10Lys), rs1688657524, gnomAD 2-203867972-G-A, CADD 1.54
- A11G (p.Ala11Gly), gnomAD rs1484954450, MetaLR 0.05, MetaSVM -1.07
- A11T (p.Ala11Thr), Ensembl rs1688657575, MetaLR 0.05, MetaSVM -1.03, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- A11P (p.Ala11Pro), gnomAD 2-203867973-G-C, MetaLR 0.09, MetaSVM -1.05
- A11A (p.Ala11Ala), gnomAD 2-203867975-T-C, CADD 4.09
- Q12* (p.Gln12Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L13L (p.Leu13Leu), rs755080468, gnomAD 2-203867979-C-T, CADD 1.99
- N14H (p.Asn14His), Ensembl rs2105772797
- N14T (p.Asn14Thr), gnomAD 2-203867983-A-C, MetaLR 0.05, MetaSVM -1.04
- N14N (p.Asn14Asn), rs376591332, gnomAD 2-203867984-C-T, CADD 0.98
- A16D (p.Ala16Asp), cosmic curated COSV55592, ExAC rs772433747, TOPMed rs772433747, gnomAD rs772433747, MetaLR 0.08, MetaSVM -1.02, Benign, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- A16T (p.Ala16Thr), ExAC rs748599835, gnomAD rs748599835, MetaLR 0.06, MetaSVM -1.02
- T17A (p.Thr17Ala), rs231775, ClinGen CA126974, cosmic curated COSV55592, ClinVar RCV000018423, MetaLR 0.00, MetaSVM -0.91, Benign, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- T17I (p.Thr17Ile), rs1484109503, ClinGen CA350137937, ClinVar RCV003048153, AlphaMissense 0.07, MetaLR 0.04, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- T17S (p.Thr17Ser), TOPMed rs1484109503, gnomAD rs1484109503, MetaLR 0.03, MetaSVM -1.03, Benign
- T17T (p.Thr17Thr), rs1688658380, gnomAD 2-203867993-C-T, CADD 3.01
- R18G (p.Arg18Gly), TOPMed rs1688658435
- R18S (p.Arg18Ser), gnomAD 2-203867996-G-C, MetaLR 0.05, MetaSVM -1.01
- T19A (p.Thr19Ala), Ensembl rs2105772830
- T19I (p.Thr19Ile), rs1323841915, ClinGen CA350137951, ClinVar RCV003871263, TOPMed rs1323841915, MetaLR 0.07, MetaSVM -1.02, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- W20* (p.Trp20Ter), rs886041906, ClinGen CA10602845, NCI-TCGA Cosmic COSV5559, NCI-TCGA Cosmic COSV9986, Pathogenic
- W20L (p.Trp20Leu), ExAC rs769368847, gnomAD rs769368847
- P21R (p.Pro21Arg), rs1041117695, ClinGen CA63785804, ClinVar RCV001039088, TOPMed rs1041117695, MetaLR 0.17, MetaSVM -0.88, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- P21S (p.Pro21Ser), cosmic curated COSV55593, gnomAD rs1688658699, MetaLR 0.05, MetaSVM -1.10, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- P21T (p.Pro21Thr), NCI-TCGA Cosmic COSV5559, cosmic curated COSV55591, gnomAD rs1688658699, Variant assessed as somatic; moderate impact.
- P21H (p.Pro21His), gnomAD 2-203868004-C-A, MetaLR 0.18, MetaSVM -0.84
- P21P (p.Pro21Pro), rs1290173158, gnomAD 2-203868005-C-G, CADD 5.08
- C22F (p.Cys22Phe), NCI-TCGA TCGA novel, Ensembl rs1581571876, MetaLR 0.04, MetaSVM -0.96, Variant assessed as somatic; moderate impact.
- C22C (p.Cys22Cys), gnomAD 2-203868008-C-T, CADD 3.32
- T23I (p.Thr23Ile), rs1365829864, ClinGen CA350137978, ClinVar RCV001349187, TOPMed rs1365829864, MetaLR 0.06, MetaSVM -1.04, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- T23N (p.Thr23Asn), TOPMed rs1365829864, gnomAD rs1365829864, MetaLR 0.06, MetaSVM -1.05, Uncertain significance
- T23P (p.Thr23Pro), gnomAD 2-203868009-A-C, MetaLR 0.05, MetaSVM -1.05
- L24P (p.Leu24Pro), gnomAD 2-203868013-T-C, MetaLR 0.06, MetaSVM -1.01
- L24H (p.Leu24His), gnomAD 2-203868013-T-A, MetaLR 0.07, MetaSVM -1.02
- L24L (p.Leu24Leu), gnomAD 2-203868014-C-T, CADD 0.35
- L25P (p.Leu25Pro), TOPMed rs1280951195, gnomAD rs1280951195, MetaLR 0.14, MetaSVM -0.96
- L25L (p.Leu25Leu), rs16840275, gnomAD 2-203868017-G-A, CADD 1.02
- F26C (p.Phe26Cys), ExAC rs748802696, gnomAD rs748802696
- F26S (p.Phe26Ser), ExAC rs748802696, gnomAD rs748802696, MetaLR 0.05, MetaSVM -1.04
- F26L (p.Phe26Leu), gnomAD 2-203868018-T-C, MetaLR 0.03, MetaSVM -0.95
- F26I (p.Phe26Ile), gnomAD 2-203868018-T-A, MetaLR 0.05, MetaSVM -1.04
- F27L (p.Phe27Leu), TOPMed rs1688660153, MetaLR 0.04, MetaSVM -1.01
- F27F (p.Phe27Phe), rs1159147215, gnomAD 2-203868023-T-C, CADD 9.17
- L28F (p.Leu28Phe), rs606231418, gnomAD 2-203868016-TG-T, CADD 13.20
- L28V (p.Leu28Val), gnomAD 2-203868024-C-G, MetaLR 0.08, MetaSVM -0.89
- L28L (p.Leu28Leu), rs1361361278, gnomAD 2-203868026-T-C, CADD 5.05
- L29V (p.Leu29Val), gnomAD 2-203868027-C-G, MetaLR 0.08, MetaSVM -1.09
- L29F (p.Leu29Phe), gnomAD 2-203868027-C-T, MetaLR 0.15, MetaSVM -0.98
- L29L (p.Leu29Leu), rs145950656, gnomAD 2-203868029-C-T, CADD 8.11
- I31V (p.Ile31Val), ExAC rs774434261, gnomAD rs774434261, MetaLR 0.06, MetaSVM -1.09
- I31I (p.Ile31Ile), rs1315404501, gnomAD 2-203868035-C-T, CADD 6.55
- P32A (p.Pro32Ala), rs369567630, ClinGen CA350138031, ClinVar RCV003989385, ESP rs369567630, AlphaMissense 0.19, MetaLR 0.18, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- P32L (p.Pro32Leu), TOPMed rs1413571467, gnomAD rs1413571467, MetaLR 0.23, MetaSVM -0.83
- P32S (p.Pro32Ser), rs369567630, ClinGen CA2067043, cosmic curated COSV10731, ClinVar RCV001060913, AlphaMissense 0.19, MetaLR 0.18, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- P32P (p.Pro32Pro), rs767441580, gnomAD 2-203868038-T-C, CADD 4.77
- V33A (p.Val33Ala), gnomAD rs1688660830
- V33I (p.Val33Ile), rs2105772910, ClinGen CA350138036, ClinVar RCV001991808, Ensembl rs2105772910, MetaLR 0.06, MetaSVM -0.99, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- V33F (p.Val33Phe), gnomAD 2-203868039-G-T, MetaLR 0.10, MetaSVM -0.97
- V33V (p.Val33Val), rs1461208141, gnomAD 2-203868041-C-T, CADD 7.38
- C35* (p.Cys35Ter), rs606231420, ClinGen CA173996, ClinVar RCV000148293, Ensembl rs606231420, CADD 34.00, Pathogenic
- C35Y (p.Cys35Tyr), NCI-TCGA Cosmic COSV5559, cosmic curated COSV55591, Variant assessed as somatic; moderate impact.
- K36N (p.Lys36Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A37T (p.Ala37Thr), gnomAD 2-203868051-G-A, MetaLR 0.24, MetaSVM -0.78
- A37A (p.Ala37Ala), gnomAD 2-203870587-A-G, CADD 8.13
- M38I (p.Met38Ile), gnomAD 2-203870590-G-A, MetaLR 0.03, MetaSVM -1.04
- H39P (p.His39Pro), TOPMed rs1293454690
- H39Y (p.His39Tyr), TOPMed rs1688711623
- H39H (p.His39His), rs760446668, gnomAD 2-203870593-C-T, CADD 0.64
- V40M (p.Val40Met), rs1553657378, ClinGen CA350138101, cosmic curated COSV55592, ClinVar RCV000604644, AlphaMissense 0.47, MetaLR 0.29, Conflicting interpretations, Inborn genetic diseases; Autoimmune lymphoproliferative syndrome due to CTLA4 ha
- Q42Q (p.Gln42Gln), rs1341891116, gnomAD 2-203870602-G-A, CADD 8.18
- P43A (p.Pro43Ala), rs1581573640, ClinGen CA350138120, ClinVar RCV001027564, ClinVar RCV005863327, AlphaMissense 0.46, MetaLR 0.50, Conflicting interpretations, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency; Inherit
- P43P (p.Pro43Pro), gnomAD 2-203870605-T-C, CADD 11.10
- A44S (p.Ala44Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A44V (p.Ala44Val), NCI-TCGA Cosmic COSV5559, cosmic curated COSV55591, Variant assessed as somatic; moderate impact.
- V45M (p.Val45Met), Ensembl rs1688712094, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- V45A (p.Val45Ala), rs767995794, gnomAD 2-203870601-AGCCT, CADD 29.90
- V46A (p.Val46Ala), rs2105775135, ClinGen CA350138140, ClinVar RCV001927170, Ensembl rs2105775135, AlphaMissense 0.36, MetaLR 0.45, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- V46I (p.Val46Ile), rs766143912, ClinGen CA2067065, ClinVar RCV001761240, ExAC rs766143912, MetaLR 0.26, MetaSVM -0.69, Uncertain significance, not provided
- V46V (p.Val46Val), rs1688712213, gnomAD 2-203870614-A-G, CADD 0.49
- L47V (p.Leu47Val), gnomAD 2-203870615-C-G, MetaLR 0.19, MetaSVM -0.93
- L47L (p.Leu47Leu), rs146200342, gnomAD 2-203870615-C-T, CADD 6.46
- A48D (p.Ala48Asp), rs2469719171, ClinGen CA350138150, ClinVar RCV002296711, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- A48V (p.Ala48Val), gnomAD 2-203870619-C-T, MetaLR 0.34, MetaSVM -0.56
- S49N (p.Ser49Asn), NCI-TCGA Cosmic COSV5559, cosmic curated COSV55592, MetaLR 0.11, MetaSVM -1.03, Variant assessed as somatic; moderate impact.
- S50S (p.Ser50Ser), gnomAD 2-203870626-C-T, CADD 4.95
- R51* (p.Arg51Ter), rs606231417, ClinGen CA173992, cosmic curated COSV10588, ClinVar RCV000148290, Pathogenic
- R51Q (p.Arg51Gln), cosmic curated COSV55592, ExAC rs759766975, gnomAD rs759766975, MetaLR 0.23, MetaSVM -0.90
- G52D (p.Gly52Asp), rs1688712533, ClinGen CA350138175, ClinVar RCV001091183, ClinVar RCV006465338, AlphaMissense 0.78, MetaLR 0.25, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency; not pro
- G52S (p.Gly52Ser), rs1216841973, ClinGen CA350138173, ClinVar RCV003749247, TOPMed rs1216841973, MetaLR 0.28, MetaSVM -0.47, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- G52V (p.Gly52Val), rs1688712533, ClinGen CA350138177, ClinVar RCV001914386, Ensembl rs1688712533, AlphaMissense 0.78, MetaLR 0.25, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- I53I (p.Ile53Ile), rs765325921, gnomAD 2-203870635-C-T, CADD 1.40
- A54P (p.Ala54Pro), rs1553657387, ClinGen CA350138185, ClinVar RCV003055780, AlphaMissense 0.38, MetaLR 0.48, Pathogenic, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- A54T (p.Ala54Thr), rs1553657387, ClinGen CA350138187, cosmic curated COSV10942, ClinVar RCV000615288, AlphaMissense 0.38, MetaLR 0.48, Conflicting interpretations, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- A54V (p.Ala54Val), NCI-TCGA Cosmic COSV5559, cosmic curated COSV55593, MetaLR 0.33, MetaSVM -0.57, Variant assessed as somatic; moderate impact.
- S55I (p.Ser55Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S55N (p.Ser55Asn), rs1688712684, ClinGen CA350138194, ClinVar RCV003748089, gnomAD rs1688712684, MetaLR 0.27, MetaSVM -0.51, Uncertain significance, Inborn genetic diseases; Autoimmune lymphoproliferative syndrome due to CTLA4 ha
- F56L (p.Phe56Leu), NCI-TCGA Cosmic COSV5559, cosmic curated COSV55593, MetaLR 0.07, MetaSVM -0.96, Variant assessed as somatic; moderate impact.
- V57M (p.Val57Met), gnomAD 2-203870645-G-A, MetaLR 0.32, MetaSVM -0.73
- V57V (p.Val57Val), rs373393185, gnomAD 2-203870647-G-A, CADD 7.50
- C58F (p.Cys58Phe), rs1581573671, ClinGen CA350138218, ClinVar RCV003074922, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- C58S (p.Cys58Ser), rs1581573671, ClinGen CA350138217, ClinVar RCV000797058, Ensembl rs1581573671, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- E59K (p.Glu59Lys), gnomAD 2-203870651-G-A, MetaLR 0.15, MetaSVM -1.00
- E59E (p.Glu59Glu), rs1581573676, gnomAD 2-203870653-G-A, CADD 16.00
- Y60F (p.Tyr60Phe), ExAC rs752811424, gnomAD rs752811424
- A61T (p.Ala61Thr), gnomAD rs1221748361, MetaLR 0.06, MetaSVM -1.00
- S62P (p.Ser62Pro), gnomAD 2-203870660-T-C, MetaLR 0.07, MetaSVM -1.02
- S62F (p.Ser62Phe), gnomAD 2-203870661-C-T, MetaLR 0.13, MetaSVM -0.98
- P63L (p.Pro63Leu), rs1688713089, ClinGen CA350138254, cosmic curated COSV10731, ClinVar RCV003588010, AlphaMissense 0.10, MetaLR 0.04, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- P63R (p.Pro63Arg), TOPMed rs1688713089, AlphaMissense 0.10, MetaLR 0.04, Uncertain significance, Inborn genetic diseases
- P63S (p.Pro63Ser), cosmic curated COSV55592, Ensembl rs1688713032, Uncertain significance, not provided
- G64D (p.Gly64Asp), ExAC rs758465752, gnomAD rs758465752
- K65E (p.Lys65Glu), gnomAD rs1346241200, MetaLR 0.23, MetaSVM -0.85
- K65R (p.Lys65Arg), rs1688713262, ClinGen CA350138265, ClinVar RCV003865569, TOPMed rs1688713262, MetaLR 0.21, MetaSVM -0.91, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- A66D (p.Ala66Asp), NCI-TCGA Cosmic COSV5559, cosmic curated COSV55593, Variant assessed as somatic; moderate impact.
- A66A (p.Ala66Ala), rs979522213, gnomAD 2-203870674-C-A, CADD 3.38
- T67T (p.Thr67Thr), rs764639840, gnomAD 2-203870677-T-G, CADD 3.18
- V69A (p.Val69Ala), ExAC rs757566658, gnomAD rs757566658, MetaLR 0.18, MetaSVM -0.80
- V69F (p.Val69Phe), cosmic curated COSV55592, 1000Genomes rs557116456, ExAC rs557116456, TOPMed rs557116456, MetaLR 0.06, MetaSVM -1.03, Uncertain significance
- V69I (p.Val69Ile), rs557116456, ClinGen CA2067072, ClinVar RCV003587319, 1000Genomes rs557116456, MetaLR 0.05, MetaSVM -1.02, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- V69V (p.Val69Val), rs1581573697, gnomAD 2-203870683-C-T, CADD 9.30
- R70Q (p.Arg70Gln), rs1581573705, ClinGen CA350138293, cosmic curated COSV10809, ClinVar RCV001027565, MetaLR 0.39, MetaSVM -0.19, Likely pathogenic, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency; Inherit
- R70W (p.Arg70Trp), rs606231422, ClinGen CA173999, cosmic curated COSV55592, ClinVar RCV000148295, MetaLR 0.48, MetaSVM 0.04, Pathogenic/Likely pathogenic, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency; not pro
- R70R (p.Arg70Arg), rs1405596225, gnomAD 2-203870686-G-A, CADD 8.06
- V71L (p.Val71Leu), rs1347670398, ClinGen CA350138298, ClinVar RCV001041748, TOPMed rs1347670398, MetaLR 0.46, MetaSVM -0.08, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- V71V (p.Val71Val), rs1688713996, gnomAD 2-203870689-G-A, CADD 10.70
- T72A (p.Thr72Ala), gnomAD rs1206369281, AlphaMissense 0.91, MetaLR 0.40, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- T72I (p.Thr72Ile), ExAC rs781579729, gnomAD rs781579729, MetaLR 0.43, MetaSVM -0.36
- T72P (p.Thr72Pro), rs1206369281, ClinGen CA350138302, ClinVar RCV000658895, gnomAD rs1206369281, AlphaMissense 0.91, MetaLR 0.40, Uncertain significance, not provided
- T72T (p.Thr72Thr), gnomAD 2-203870692-A-C, CADD 2.03
- V73L (p.Val73Leu), gnomAD 2-203870693-G-C, MetaLR 0.08, MetaSVM -1.01
- V73V (p.Val73Val), rs866679318, gnomAD 2-203870695-G-T, CADD 8.86
- L74I (p.Leu74Ile), gnomAD 2-203870696-C-A, MetaLR 0.30, MetaSVM -0.66
- R75L (p.Arg75Leu), 1000Genomes rs1196646336, gnomAD rs1196646336, MetaLR 0.39, MetaSVM -0.39, Uncertain significance
- R75Q (p.Arg75Gln), rs1196646336, ClinGen CA350138321, cosmic curated COSV10731, ClinVar RCV001213474, MetaLR 0.23, MetaSVM -0.78, Uncertain significance, not provided; Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffic
- R75W (p.Arg75Trp), rs1688714312, ClinGen CA350138320, NCI-TCGA Cosmic COSV5559, cosmic curated COSV55592, MetaLR 0.50, MetaSVM -0.20, Pathogenic, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- R75R (p.Arg75Arg), rs1553657396, gnomAD 2-203870701-G-T, CADD 7.36
- Q76* (p.Gln76Ter), rs1688714490, ClinGen CA350138326, ClinVar RCV001331373, Ensembl rs1688714490, Pathogenic
- Q76H (p.Gln76His), rs2469719303, ClinGen CA350138330, ClinVar RCV003151496, Uncertain significance, not specified
- Q76L (p.Gln76Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q76K (p.Gln76Lys), gnomAD 2-203870702-C-A, MetaLR 0.13, MetaSVM -0.93
- A77T (p.Ala77Thr), rs1378866958, ClinGen CA350138332, cosmic curated COSV55592, ClinVar RCV003748635, MetaLR 0.08, MetaSVM -1.02, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- A77A (p.Ala77Ala), rs1478283146, gnomAD 2-203870707-T-C, CADD 0.13
- D78D (p.Asp78Asp), gnomAD 2-203870710-C-T, CADD 2.76
- S79I (p.Ser79Ile), ExAC rs754725143, TOPMed rs754725143, gnomAD rs754725143, MetaLR 0.10, MetaSVM -0.98
- S79N (p.Ser79Asn), ExAC rs754725143, TOPMed rs754725143, gnomAD rs754725143, MetaLR 0.06, MetaSVM -1.05
- Q80* (p.Gln80Ter), rs1688714703, ClinGen CA350138355, ClinVar RCV001997536, TOPMed rs1688714703, AlphaMissense 0.07, MetaLR 0.10, Pathogenic
- Q80E (p.Gln80Glu), rs1688714703, ClinGen CA350138354, ClinVar RCV002295963, AlphaMissense 0.07, MetaLR 0.10, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- Q80K (p.Gln80Lys), TOPMed rs1688714703, Pathogenic
- Q80Q (p.Gln80Gln), rs778678737, gnomAD 2-203870716-G-A, CADD 0.99
- V81G (p.Val81Gly), Ensembl rs1581573749
- V81L (p.Val81Leu), TOPMed rs1431375309, gnomAD rs1431375309, MetaLR 0.09, MetaSVM -1.06
- V81M (p.Val81Met), TOPMed rs1431375309, gnomAD rs1431375309, MetaLR 0.06, MetaSVM -1.04
- V81V (p.Val81Val), gnomAD 2-203870719-G-T, CADD 5.79
- T82I (p.Thr82Ile), Ensembl rs1688714855
- T82S (p.Thr82Ser), Ensembl rs1688714855, MetaLR 0.20, MetaSVM -0.91
- T82N (p.Thr82Asn), gnomAD 2-203870721-C-A, MetaLR 0.27, MetaSVM -0.83
- T82T (p.Thr82Thr), rs139154557, gnomAD 2-203870722-T-C, CADD 6.20
- V84I (p.Val84Ile), rs1422926559, ClinGen CA350138381, ClinVar RCV004374919, TOPMed rs1422926559, AlphaMissense 0.08, MetaLR 0.09, Uncertain significance, Inborn genetic diseases
- C85S (p.Cys85Ser), rs2105775283, ClinGen CA350138392, ClinVar RCV003038501, AlphaMissense 0.97, MetaLR 0.47, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- C85W (p.Cys85Trp), rs1688715115, ClinGen CA350138394, cosmic curated COSV55591, ClinVar RCV001225872, AlphaMissense 0.98, MetaLR 0.37, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- C85Y (p.Cys85Tyr), rs2105775283, ClinGen CA350138391, ClinVar RCV001904295, Ensembl rs2105775283, AlphaMissense 0.97, MetaLR 0.47, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- C85C (p.Cys85Cys), gnomAD 2-203870731-T-C, CADD 6.43
- A86G (p.Ala86Gly), rs376038796, ClinGen CA350138398, ClinVar RCV002009585, 1000Genomes rs376038796, AlphaMissense 0.27, MetaLR 0.49, Uncertain significance, Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency
- A86T (p.Ala86Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
Public CTLA4 analysis runs
- CTLA4 analysis run — CTLA4 (474 variants) — completed 2026-08-19