MPL (Thrombopoietin receptor) variants and mutations
MPL (also known as Thrombopoietin receptor) is a human protein-coding gene encoding a thrombopoietin receptor protein. Thrombopoietin signaling through this pathway drives megakaryocyte maturation, platelet production, and hematopoietic stem-cell maintenance. Activating variants can cause myeloproliferative neoplasms or hereditary thrombocytosis, whereas loss-of-function variants cause congenital amegakaryocytic thrombocytopenia. This analysis covers 1,464 MPL variants and mutations. Of these, 81% have computational variant effect predictions. Disease context includes congenital amegakaryocytic thrombocytopenia 1, thrombocythemia 2, and congenital amegakaryocytic thrombocytopenia. Example MPL variants include P2A, P2L, and P2S.
Variant analysis overview
- Gene: MPL
- Protein: Thrombopoietin receptor
- UniProt accession: P40238
- Organism: Homo sapiens
- Variants analyzed: 1464
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,219 unspecified-consequence records; 103 missense variants; 105 synonymous variants; 21 frameshift variants; 4 splice-region variants; 3 in-frame deletions; 3 stop-gained variants; 1 in-frame insertions; 5 substitution
- Prediction scores: 1,190 variants have prediction scores (81% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: congenital amegakaryocytic thrombocytopenia 1, thrombocythemia 2, congenital amegakaryocytic thrombocytopenia, Thrombocytopenia, primary myelofibrosis, essential thrombocythemia, autoimmune thrombocytopenic purpura, aplastic anemia, hemorrhage, chronic hepatitis C virus infection, severe aplastic anemia, thrombocytopenic purpura.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 2 domains; 7 post-translational modification sites.
- Structural context: 495 variants have structural context.
- PTM context: 12 variants overlap post-translational modification sites.
- Experimental data: 49 protein positions have experimental scores. Source: TpoR activation by low dosage of Tpo, TpoR activation by low dosage of romi-peptide, TpoR activation by low dosage of eltrombopag.
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, ClinGen, MaveDB, LitVar.
Notable MPL variants
Examples include P2A, P2L, P2S, P2H, P2P, S3F, S3Y, S3S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- P2A (p.Pro2Ala), ExAC rs763338238, gnomAD rs763338238, REVEL 0.41, MetaLR 0.67
- P2L (p.Pro2Leu), 1000Genomes rs188798468, ExAC rs188798468, TOPMed rs188798468, gnomAD rs188798468, REVEL 0.53, MetaLR 0.72
- P2S (p.Pro2Ser), ExAC rs763338238, gnomAD rs763338238, REVEL 0.39, MetaLR 0.71
- P2H (p.Pro2His), gnomAD 1-43337853-C-A, REVEL 0.46, MetaLR 0.72
- P2P (p.Pro2Pro), rs2153916091, gnomAD 1-43337854-C-T, CADD 10.70
- S3F (p.Ser3Phe), gnomAD 1-43337856-C-T, REVEL 0.13, MetaLR 0.28
- S3Y (p.Ser3Tyr), gnomAD 1-43337856-C-A, REVEL 0.25, MetaLR 0.28
- S3S (p.Ser3Ser), gnomAD 1-43337857-C-G, CADD 7.11
- W4* (p.Trp4Ter), rs1647004673, ClinGen CA339971854, ClinVar RCV001837551, Ensembl rs1647004673, CADD 37.00, Uncertain significance
- W4R (p.Trp4Arg), rs752112087, ClinGen CA806549, NCI-TCGA Cosmic COSV6524, cosmic curated COSV65244, REVEL 0.63, MetaLR 0.68, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia
- W4L (p.Trp4Leu), gnomAD 1-43337859-G-T, REVEL 0.50, MetaLR 0.71
- W4C (p.Trp4Cys), gnomAD 1-43337860-G-C, REVEL 0.70, MetaLR 0.69
- A5S (p.Ala5Ser), TOPMed rs1356606287, gnomAD rs1356606287, MetaLR 0.48, MetaSVM -0.53
- A5T (p.Ala5Thr), TOPMed rs1356606287, gnomAD rs1356606287, REVEL 0.31, MetaLR 0.48
- A5D (p.Ala5Asp), gnomAD 1-43337862-C-A, REVEL 0.44, MetaLR 0.51
- L6F (p.Leu6Phe), gnomAD 1-43337864-C-T, REVEL 0.42, MetaLR 0.56
- L6L (p.Leu6Leu), rs1209678224, gnomAD 1-43337866-C-A, CADD 8.92
- F7F (p.Phe7Phe), gnomAD 1-43337869-C-T, CADD 7.74
- M8L (p.Met8Leu), 1000Genomes rs572208458, ExAC rs572208458, TOPMed rs572208458, gnomAD rs572208458, MetaLR 0.15, MetaSVM -0.97, Uncertain significance, Inborn genetic diseases
- M8R (p.Met8Arg), gnomAD rs1557462638, REVEL 0.46, MetaLR 0.27
- M8V (p.Met8Val), rs572208458, ClinGen CA806551, ClinVar RCV001912713, 1000Genomes rs572208458, REVEL 0.22, MetaLR 0.17, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia
- M8T (p.Met8Thr), gnomAD 1-43337871-T-C, REVEL 0.17, MetaLR 0.27
- V9L (p.Val9Leu), Ensembl rs2153916099, MetaLR 0.39, MetaSVM -0.69
- V9I (p.Val9Ile), gnomAD 1-43337873-G-A, REVEL 0.24, MetaLR 0.42
- V9V (p.Val9Val), rs1343948119, gnomAD 1-43337875-C-A, CADD 9.31
- T10A (p.Thr10Ala), gnomAD 1-43337876-A-G, REVEL 0.08, MetaLR 0.31
- T10I (p.Thr10Ile), gnomAD 1-43337877-C-T, REVEL 0.09, MetaLR 0.31
- S11F (p.Ser11Phe), gnomAD rs1449272010
- S11P (p.Ser11Pro), 1000Genomes rs2153916103, REVEL 0.43, MetaLR 0.53
- S11S (p.Ser11Ser), rs1194559296, gnomAD 1-43337881-C-T, CADD 10.80
- C12Y (p.Cys12Tyr), Ensembl rs2153916105, REVEL 0.35, MetaLR 0.33
- C12C (p.Cys12Cys), rs2153916106, gnomAD 1-43337884-C-T, CADD 10.50
- L13I (p.Leu13Ile), Ensembl rs2153916107, MetaLR 0.64, MetaSVM -0.17
- L13P (p.Leu13Pro), gnomAD 1-43337886-T-C, REVEL 0.71, MetaLR 0.67
- L14F (p.Leu14Phe), TOPMed rs1557462648, REVEL 0.14, MetaLR 0.34
- L15P (p.Leu15Pro), gnomAD rs1263040078, REVEL 0.23, MetaLR 0.31
- L15M (p.Leu15Met), gnomAD 1-43337891-C-A, REVEL 0.32, MetaLR 0.42
- L15L (p.Leu15Leu), gnomAD 1-43337893-G-T, CADD 8.85
- A16P (p.Ala16Pro), 1000Genomes rs541014818
- A16T (p.Ala16Thr), 1000Genomes rs541014818, REVEL 0.13, MetaLR 0.26
- A16V (p.Ala16Val), gnomAD rs1476891431, MetaLR 0.25, MetaSVM -0.91
- P17L (p.Pro17Leu), cosmic curated COSV10468, gnomAD rs1190077369
- P17S (p.Pro17Ser), rs1647004869, ClinGen CA339972099, cosmic curated COSV10529, ClinVar RCV001102211, AlphaMissense 0.09, MetaLR 0.24, Uncertain significance, Congenital amegakaryocytic thrombocytopenia
- P17T (p.Pro17Thr), gnomAD rs1647004869, REVEL 0.22, AlphaMissense 0.09, Uncertain significance
- P17P (p.Pro17Pro), rs2153916114, gnomAD 1-43337899-T-C, CADD 10.00
- Q18E (p.Gln18Glu), gnomAD 1-43337900-C-G, REVEL 0.17, MetaLR 0.32
- N19K (p.Asn19Lys), rs752706183, ClinGen CA806552, ClinVar RCV002852457, ClinVar RCV002875591, REVEL 0.17, MetaLR 0.32, Conflicting interpretations, Inborn genetic diseases; Congenital amegakaryocytic thrombocytopenia; Essential
- N19T (p.Asn19Thr), rs2153916116, gnomAD 1-43337900-CA-C, CADD 21.50
- N19N (p.Asn19Asn), gnomAD 1-43337905-C-T, CADD 8.85
- L20L (p.Leu20Leu), rs756165019, gnomAD 1-43337908-G-A, CADD 9.44
- A21D (p.Ala21Asp), Ensembl rs2153916121
- A21T (p.Ala21Thr), gnomAD rs1162488972, MetaLR 0.26, MetaSVM -0.78
- A21V (p.Ala21Val), NCI-TCGA Cosmic COSV6524, cosmic curated COSV65246, Ensembl rs2153916121, REVEL 0.17, MetaLR 0.29, Variant assessed as somatic; moderate impact.
- A21S (p.Ala21Ser), gnomAD 1-43337909-G-T, REVEL 0.18, MetaLR 0.29
- Q22* (p.Gln22Ter), cosmic curated COSV10890, Ensembl rs2153916123
- V23A (p.Val23Ala), Ensembl rs2153916124
- V23D (p.Val23Asp), Ensembl rs2153916124, MetaLR 0.29, MetaSVM -0.56
- V23V (p.Val23Val), gnomAD 1-43337917-C-T, CADD 11.30
- S24N (p.Ser24Asn), Ensembl rs2153916127, MetaLR 0.14, MetaSVM -0.93
- S25N (p.Ser25Asn), Ensembl rs2153916128, MetaLR 0.70, MetaSVM 0.01
- S25T (p.Ser25Thr), gnomAD 1-43337922-G-C, REVEL 0.48, MetaLR 0.69
- Q26K (p.Gln26Lys), gnomAD 1-43337924-C-A, REVEL 0.27, MetaLR 0.44
- D27E (p.Asp27Glu), gnomAD rs1647006325, REVEL 0.10, MetaLR 0.32
- V28V (p.Val28Val), gnomAD 1-43338103-C-T, CADD 8.81
- S29L (p.Ser29Leu), rs752416111, gnomAD 1-43338101-GTC-G, CADD 24.30
- L30* (p.Leu30Ter), rs2545673631, ClinGen CA339972491, ClinVar RCV003803808, Pathogenic
- L30S (p.Leu30Ser), rs2545673631, ClinGen CA339972495, ClinVar RCV003793243, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia
- L31P (p.Leu31Pro), rs878854771, ClinGen CA10581793, ClinVar RCV000228735, Ensembl rs878854771, AlphaMissense 0.13, MetaLR 0.34, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Thrombocythemia 1
- A32T (p.Ala32Thr), rs746914831, ClinGen CA806578, ClinVar RCV003807081, ExAC rs746914831, REVEL 0.16, MetaLR 0.26, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia
- A32V (p.Ala32Val), rs886046348, ClinGen CA10610273, ClinVar RCV000304665, ClinVar RCV004537669, REVEL 0.30, MetaLR 0.37, Uncertain significance, MPL-related disorder; Congenital amegakaryocytic thrombocytopenia
- A32H (p.Ala32His), rs2153916214, gnomAD 1-43338111-TG-T, CADD 29.90
- S33* (p.Ser33Ter), rs1228227826, Ensembl rs1228227826, ClinGen CA339972534, ClinVar RCV001263971, CADD 28.50, Likely pathogenic
- S33T (p.Ser33Thr), Ensembl rs2153916218
- D34G (p.Asp34Gly), gnomAD 1-43338120-A-G, REVEL 0.16, MetaLR 0.28
- D34E (p.Asp34Glu), gnomAD 1-43338121-C-G, REVEL 0.11, MetaLR 0.22
- S35* (p.Ser35Ter), Ensembl rs2153916222
- S35A (p.Ser35Ala), gnomAD rs1253003822, REVEL 0.07, MetaLR 0.16
- S35P (p.Ser35Pro), gnomAD 1-43338122-T-C, REVEL 0.04, MetaLR 0.02
- E36Q (p.Glu36Gln), gnomAD rs1647006474, REVEL 0.39, MetaLR 0.57
- E36V (p.Glu36Val), Ensembl rs2153916228, MetaLR 0.62, MetaSVM 0.37
- E36G (p.Glu36Gly), gnomAD 1-43338126-A-G, REVEL 0.55, MetaLR 0.59
- P37A (p.Pro37Ala), Ensembl rs2153916231, MetaLR 0.24, MetaSVM -0.82
- P37L (p.Pro37Leu), gnomAD 1-43338129-C-T, REVEL 0.12, MetaLR 0.20
- P37P (p.Pro37Pro), rs142697469, gnomAD 1-43338130-C-T, CADD 8.48
- L38L (p.Leu38Leu), gnomAD 1-43338131-C-T, CADD 9.41
- K39N (p.Lys39Asn), rs17292650, ClinGen CA123787, cosmic curated COSV65244, ClinVar RCV000015225, REVEL 0.23, MetaLR 0.06, Benign/Likely benign, Essential thrombocythemia; Congenital amegakaryocytic thrombocytopenia; not spec
- C40S (p.Cys40Ser), gnomAD 1-43338137-T-A, REVEL 0.92, MetaLR 0.97
- C40C (p.Cys40Cys), rs747864027, gnomAD 1-43338139-T-C, CADD 10.10
- F41L (p.Phe41Leu), ExAC rs769423189, gnomAD rs769423189, REVEL 0.75, MetaLR 0.77, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia
- S42Y (p.Ser42Tyr), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10099, Variant assessed as somatic; moderate impact.
- S42F (p.Ser42Phe), gnomAD 1-43338144-C-T, REVEL 0.69, MetaLR 0.73
- S42S (p.Ser42Ser), rs1647006574, gnomAD 1-43338145-C-T, CADD 9.65
- R43* (p.Arg43Ter), rs148434485, ClinGen CA806582, cosmic curated COSV65245, ClinVar RCV000411190, CADD 36.00, Pathogenic
- R43P (p.Arg43Pro), cosmic curated COSV65246, ESP rs147938568, ExAC rs147938568, TOPMed rs147938568, MetaLR 0.60, MetaSVM 0.05
- R43Q (p.Arg43Gln), rs147938568, cosmic curated COSV65245, NCI-TCGA Cosmic COSV6524, ESP rs147938568, REVEL 0.29, MetaLR 0.31, Conflicting interpretations, Essential thrombocythemia; Congenital amegakaryocytic thrombocytopenia; Inborn g
- T44I (p.Thr44Ile), rs772445486, ClinGen CA806584, ClinVar RCV002264883, ClinVar RCV004534016, REVEL 0.43, MetaLR 0.42, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia; MPL-rela
- F45L (p.Phe45Leu), ExAC rs775885799, TOPMed rs775885799, gnomAD rs775885799, REVEL 0.25, MetaLR 0.29
- F45S (p.Phe45Ser), ESP rs145714475, ExAC rs145714475, TOPMed rs145714475, gnomAD rs145714475, REVEL 0.55, MetaLR 0.44
- F45C (p.Phe45Cys), gnomAD 1-43338153-T-G, REVEL 0.61, MetaLR 0.44
- E46K (p.Glu46Lys), rs1398260614, ClinGen CA339972739, ClinVar RCV002962150, TOPMed rs1398260614, REVEL 0.54, AlphaMissense 0.32, Uncertain significance, Essential thrombocythemia; Congenital amegakaryocytic thrombocytopenia
- E46Q (p.Glu46Gln), rs1398260614, ClinGen CA339972740, ClinVar RCV003788902, AlphaMissense 0.32, MetaLR 0.48, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia
- E46G (p.Glu46Gly), gnomAD 1-43338156-A-G, REVEL 0.74, MetaLR 0.51
- D47N (p.Asp47Asn), Ensembl rs2153916242, MetaLR 0.78, MetaSVM 0.66
- D47T (p.Asp47Thr), rs1447038536, gnomAD 1-43338156-AG-A, CADD 26.90
- D47D (p.Asp47Asp), rs1647006717, gnomAD 1-43338160-C-T, CADD 8.46
- L48F (p.Leu48Phe), Ensembl rs2153916243
- L48I (p.Leu48Ile), NCI-TCGA Cosmic COSV6524, cosmic curated COSV65247, MetaLR 0.52, MetaSVM 0.15, Variant assessed as somatic; moderate impact.
- L48H (p.Leu48His), gnomAD 1-43338162-T-A, REVEL 0.78, MetaLR 0.56
- T49A (p.Thr49Ala), rs764333753, ClinGen CA806587, ClinVar RCV001310848, ClinVar RCV005213520, REVEL 0.71, MetaLR 0.74, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia; not prov
- T49N (p.Thr49Asn), cosmic curated COSV10822, Ensembl rs2153916246, MetaLR 0.75, MetaSVM 0.61
- C50Y (p.Cys50Tyr), gnomAD 1-43338168-G-A, REVEL 0.94, MetaLR 0.98
- C50F (p.Cys50Phe), gnomAD 1-43338168-G-T, REVEL 0.94, MetaLR 0.98
- C50C (p.Cys50Cys), rs1647006757, gnomAD 1-43338169-C-T, CADD 11.80
- F51I (p.Phe51Ile), Ensembl rs2153916248, MetaLR 0.80, MetaSVM 0.74
- F51Y (p.Phe51Tyr), gnomAD 1-43338163-C-CACT, CADD 26.80
- W52* (p.Trp52Ter), rs2545673744, cosmic curated COSV10529, NCI-TCGA TCGA novel, ClinGen CA339972846, CADD 37.00, Likely pathogenic
- W52C (p.Trp52Cys), Ensembl rs1647006772
- W52R (p.Trp52Arg), rs2153916250, ClinGen CA339972841, ClinVar RCV004493708, Ensembl rs2153916250, AlphaMissense 0.96, MetaLR 0.88, Uncertain significance, Inborn genetic diseases
- D53D (p.Asp53Asp), rs753950108, gnomAD 1-43338178-T-C, CADD 9.09
- E54K (p.Glu54Lys), Ensembl rs1570464280, REVEL 0.43, MetaLR 0.44
- E54A (p.Glu54Ala), gnomAD 1-43338180-A-C, REVEL 0.44, MetaLR 0.26
- E54E (p.Glu54Glu), rs761922496, gnomAD 1-43338181-G-A, CADD 8.20
- E56Q (p.Glu56Gln), NCI-TCGA Cosmic COSV6524, cosmic curated COSV65244, MetaLR 0.33, MetaSVM -0.34, Variant assessed as somatic; moderate impact.
- A57T (p.Ala57Thr), NCI-TCGA Cosmic COSV6524, cosmic curated COSV65245, Ensembl rs2153916256, Variant assessed as somatic; moderate impact.
- A57V (p.Ala57Val), Ensembl rs2153916258, MetaLR 0.49, MetaSVM -0.47
- A58E (p.Ala58Glu), NCI-TCGA TCGA novel, 1000Genomes rs6087, ExAC rs6087, TOPMed rs6087, REVEL 0.07, MetaLR 0.14, Likely benign
- A58G (p.Ala58Gly), 1000Genomes rs6087, ExAC rs6087, TOPMed rs6087, gnomAD rs6087, Likely benign
- A58T (p.Ala58Thr), Ensembl rs2153916260, MetaLR 0.17, MetaSVM -0.93
- A58V (p.Ala58Val), rs6087, ClinGen CA806590, cosmic curated COSV10099, ClinVar RCV001272210, REVEL 0.10, MetaLR 0.15, Conflicting interpretations, Essential thrombocythemia; Congenital amegakaryocytic thrombocytopenia; Congenit
- A58A (p.Ala58Ala), rs141077413, gnomAD 1-43338193-G-A, CADD 0.43
- P59R (p.Pro59Arg), TOPMed rs1036288400, REVEL 0.32, MetaLR 0.40
- P59S (p.Pro59Ser), TOPMed rs543174329, REVEL 0.24, MetaLR 0.40
- P59L (p.Pro59Leu), gnomAD 1-43338195-C-T, REVEL 0.33, MetaLR 0.39
- S60G (p.Ser60Gly), TOPMed rs940757489, gnomAD rs940757489, REVEL 0.14, MetaLR 0.16, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia
- S60N (p.Ser60Asn), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10099, MetaLR 0.13, MetaSVM -1.02, Variant assessed as somatic; moderate impact.
- G61E (p.Gly61Glu), gnomAD 1-43338201-G-A, REVEL 0.17, MetaLR 0.28
- G61V (p.Gly61Val), gnomAD 1-43338201-G-T, REVEL 0.46, MetaLR 0.54
- G61G (p.Gly61Gly), rs1253127338, gnomAD 1-43338202-G-A, CADD 4.17
- T62I (p.Thr62Ile), rs201727975, ClinGen CA806592, ClinVar RCV001578625, ClinVar RCV001751802, REVEL 0.06, MetaLR 0.11, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; not specified; not provided
- T62R (p.Thr62Arg), 1000Genomes rs201727975, ESP rs201727975, ExAC rs201727975, TOPMed rs201727975, MetaLR 0.23, MetaSVM -0.88, Uncertain significance
- T62K (p.Thr62Lys), gnomAD 1-43338204-C-A, REVEL 0.12, MetaLR 0.17
- T62T (p.Thr62Thr), rs1198287213, gnomAD 1-43338205-A-T, CADD 1.89
- Y63* (p.Tyr63Ter), rs1373623383, ClinGen CA339973030, ClinVar RCV001174802, ClinVar RCV001819878, CADD 35.00, Pathogenic
- Y63H (p.Tyr63His), ExAC rs766172846, TOPMed rs766172846, gnomAD rs766172846, REVEL 0.63, MetaLR 0.76, Uncertain significance, Essential thrombocythemia; Congenital amegakaryocytic thrombocytopenia; Inborn g
- Y63N (p.Tyr63Asn), gnomAD 1-43338206-T-A, REVEL 0.76, MetaLR 0.77
- Q64* (p.Gln64Ter), rs2153916273, ClinGen CA339973040, ClinVar RCV002002275, NCI-TCGA TCGA novel, CADD 37.00, Pathogenic
- L65M (p.Leu65Met), Ensembl rs2153916274, MetaLR 0.58, MetaSVM -0.33
- L66L (p.Leu66Leu), rs886046349, gnomAD 1-43338215-C-T, CADD 10.90
- A68D (p.Ala68Asp), TOPMed rs1647007342
- A68S (p.Ala68Ser), Ensembl rs1647007321, REVEL 0.29, MetaLR 0.36, Uncertain significance, Inborn genetic diseases
- A68T (p.Ala68Thr), cosmic curated COSV65247, Ensembl rs1647007321, REVEL 0.34, MetaLR 0.39
- A68V (p.Ala68Val), TOPMed rs1647007342, MetaLR 0.44, MetaSVM -0.01
- Y69C (p.Tyr69Cys), rs2545673818, ClinGen CA339973122, ClinVar RCV002303247, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia
- Y69H (p.Tyr69His), rs1439788842, ClinGen CA339973116, ClinVar RCV003154843, TOPMed rs1439788842, REVEL 0.51, MetaLR 0.42, Pathogenic, Congenital amegakaryocytic thrombocytopenia
- Y69N (p.Tyr69Asn), TOPMed rs1439788842, MetaLR 0.37, MetaSVM -0.45, Pathogenic
- P70L (p.Pro70Leu), rs61754776, ClinGen CA160813, cosmic curated COSV65246, ClinVar RCV000121534, REVEL 0.14, MetaLR 0.21, Likely benign, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia; not spec
- P70R (p.Pro70Arg), rs2545673821, ClinGen CA2580062786, ClinVar RCV002852989, Pathogenic
- P70Q (p.Pro70Gln), gnomAD 1-43338228-C-A, REVEL 0.05, MetaLR 0.18
- P70P (p.Pro70Pro), rs6086, gnomAD 1-43338229-G-A, CADD 8.90
- R71=, rs780738649, NCI-TCGA Cosmic COSV1009, NCI-TCGA Cosmic COSV6524, AlphaMissense 0.15, MetaLR 0.07, Variant assessed as somatic; low impact.
- R71L (p.Arg71Leu), 1000Genomes rs368753117, ESP rs368753117, ExAC rs368753117, TOPMed rs368753117, REVEL 0.12, MetaLR 0.16, Uncertain significance
- R71Q (p.Arg71Gln), rs368753117, ClinGen CA806595, ClinVar RCV001834759, ClinVar RCV002490971, REVEL 0.10, MetaLR 0.14, Uncertain significance, Essential thrombocythemia; Congenital amegakaryocytic thrombocytopenia; Primary
- R71W (p.Arg71Trp), cosmic curated COSV65244, ExAC rs780738649, TOPMed rs780738649, gnomAD rs780738649, REVEL 0.12, AlphaMissense 0.15, Uncertain significance, Essential thrombocythemia; Congenital amegakaryocytic thrombocytopenia
- R71R (p.Arg71Arg), rs780738649, gnomAD 1-43338230-C-A, AlphaMissense 0.15, MetaLR 0.07
- E72* (p.Glu72Ter), rs1406715863, ClinGen CA339973225, ClinVar RCV001263972, ClinVar RCV001383285, AlphaMissense 0.27, MetaLR 0.73, Pathogenic
- E72D (p.Glu72Asp), Ensembl rs2153916421, MetaLR 0.58, MetaSVM -0.31
- E72Q (p.Glu72Gln), gnomAD rs1406715863, REVEL 0.57, AlphaMissense 0.27, Pathogenic
- K73K (p.Lys73Lys), rs748957880, gnomAD 1-43338548-G-A, CADD 9.12
- P74L (p.Pro74Leu), gnomAD 1-43338550-C-T, REVEL 0.41, MetaLR 0.54
- R75C (p.Arg75Cys), rs756918176, NCI-TCGA Cosmic COSV6524, cosmic curated COSV65247, ExAC rs756918176, REVEL 0.65, MetaLR 0.64, Uncertain significance, Essential thrombocythemia; Congenital amegakaryocytic thrombocytopenia
- R75H (p.Arg75His), rs148276667, ClinGen CA806618, NCI-TCGA Cosmic COSV6524, cosmic curated COSV65247, REVEL 0.49, MetaLR 0.63, Uncertain significance, Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia
- R75P (p.Arg75Pro), ESP rs148276667, ExAC rs148276667, TOPMed rs148276667, gnomAD rs148276667, REVEL 0.62, MetaLR 0.63, Uncertain significance
- A76V (p.Ala76Val), Ensembl rs2153916426, MetaLR 0.12, MetaSVM -1.02
- A76T (p.Ala76Thr), gnomAD 1-43338555-G-A, REVEL 0.04, MetaLR 0.10
- A76D (p.Ala76Asp), gnomAD 1-43338556-C-A, REVEL 0.04, MetaLR 0.17
- A76A (p.Ala76Ala), rs1398497408, gnomAD 1-43338557-T-C, CADD 8.54
- C77S (p.Cys77Ser), rs1291157023, gnomAD 1-43338558-TG-T, CADD 31.00
- C77Y (p.Cys77Tyr), gnomAD 1-43338559-G-A, REVEL 0.90, MetaLR 0.92
- C77C (p.Cys77Cys), rs747378368, gnomAD 1-43338560-C-T, CADD 9.29
- P78H (p.Pro78His), Ensembl rs2153916435
Public MPL analysis runs
- MPL analysis run — MPL (1,464 variants) — completed 2026-08-18