MYD88 (Q99836) variants and mutations
MYD88 (also known as Q99836) is a human protein-coding gene encoding a myeloid differentiation primary response protein. It relays signals from most Toll-like receptors and IL-1-family receptors to NF-kappaB and other inflammatory pathways. Loss-of-function variants impair innate immune defense, while the recurrent L265P gain-of-function variant drives several B-cell malignancies. This analysis covers 1,230 MYD88 variants and mutations. Of these, 42% have computational variant effect predictions. Disease context includes pyogenic bacterial infections due to MyD88 deficiency, B-cell chronic lymphocytic leukemia, and diffuse large B-cell lymphoma. Example MYD88 variants include A2T, A2S, and A3T.
Variant analysis overview
- Gene: MYD88
- Protein: Q99836
- UniProt accession: Q99836
- Organism: Homo sapiens
- Variants analyzed: 1230
- Variant scope: all variants
- Completed: 2026-08-10
Variant and mutation evidence
- Variant composition: 1,009 unspecified-consequence records; 75 missense variants; 11 frameshift variants; 119 synonymous variants; 5 in-frame deletions; 6 stop-gained variants; 1 splice acceptor variant; 4 substitution
- Prediction scores: 516 variants have prediction scores (42% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: pyogenic bacterial infections due to MyD88 deficiency, B-cell chronic lymphocytic leukemia, diffuse large B-cell lymphoma, lymphoid leukemia, inborn error of immunity, Waldenstrom macroglobulinemia, primary central nervous system lymphoma, Immunodeficiency due to interleukin-1 receptor-associated kinase-4 deficiency, B-cell non-Hodgkin lymphoma, lymphoplasmacytic lymphoma, non-Hodgkin lymphoma, breast diffuse large B-cell lymphoma.
Protein structure and variant hotspots
- Protein features: 2 domains; 1 post-translational modification sites.
- Structural context: 805 variants have structural context.
- PTM context: 5 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 MYD88 variants
Examples include A2T, A2S, A3T, A3V, A3A, G4R, G4V, G5D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2T (p.Ala2Thr), gnomAD rs1167556183, CADD 18.20, PolyPhen-2 0.07
- A2S (p.Ala2Ser), gnomAD 3-38138704-G-T, CADD 12.30, PolyPhen-2 0.00
- A3T (p.Ala3Thr), Ensembl rs2125775141
- A3V (p.Ala3Val), ExAC rs779461452, gnomAD rs779461452, CADD 14.00, PolyPhen-2 0.00
- A3A (p.Ala3Ala), rs1700985540, gnomAD 3-38138709-A-G, CADD 7.13
- G4R (p.Gly4Arg), cosmic curated COSV10589, Ensembl rs752325925, CADD 16.80, PolyPhen-2 0.09
- G4V (p.Gly4Val), TOPMed rs1162844242, gnomAD rs1162844242, AlphaMissense 0.99, MetaLR 0.08
- G5D (p.Gly5Asp), ESP rs371896760, ExAC rs371896760, TOPMed rs371896760, gnomAD rs371896760
- G5S (p.Gly5Ser), cosmic curated COSV10589, Ensembl rs2125775169
- G5V (p.Gly5Val), ESP rs371896760, ExAC rs371896760, TOPMed rs371896760, gnomAD rs371896760, CADD 0.14, PolyPhen-2 0.00
- P6L (p.Pro6Leu), Ensembl rs1700986467, CADD 17.30
- P6S (p.Pro6Ser), cosmic curated COSV57182, TOPMed rs1300885784, gnomAD rs1300885784, CADD 5.50, PolyPhen-2 0.00
- P6T (p.Pro6Thr), TOPMed rs1300885784, gnomAD rs1300885784
- P6P (p.Pro6Pro), rs2125775196, gnomAD 3-38138718-C-T, CADD 3.75
- G7A (p.Gly7Ala), Ensembl rs2125775205
- G7D (p.Gly7Asp), Ensembl rs2125775205
- G7V (p.Gly7Val), Ensembl rs2125775205, CADD 0.12, PolyPhen-2 0.00
- G7S (p.Gly7Ser), gnomAD 3-38138719-G-A, CADD 0.64, PolyPhen-2 0.00
- G7G (p.Gly7Gly), gnomAD 3-38138721-C-A, CADD 5.86
- A8E (p.Ala8Glu), 1000Genomes rs533607667
- A8P (p.Ala8Pro), gnomAD rs1700986561
- A8T (p.Ala8Thr), gnomAD rs1700986561, AlphaMissense 0.29, MetaLR 0.02
- A8V (p.Ala8Val), 1000Genomes rs533607667, CADD 3.00, PolyPhen-2 0.00
- A8A (p.Ala8Ala), gnomAD 3-38138724-G-A, AlphaMissense 0.11, MetaLR 0.01
- G9A (p.Gly9Ala), Ensembl rs905392063
- G9E (p.Gly9Glu), Ensembl rs905392063, CADD 2.40, PolyPhen-2 0.00
- G9V (p.Gly9Val), Ensembl rs905392063
- G9G (p.Gly9Gly), rs2125775230, gnomAD 3-38138727-G-A, CADD 5.84
- S10A (p.Ser10Ala), Ensembl rs1575273361, CADD 8.98, PolyPhen-2 0.00
- S10C (p.Ser10Cys), gnomAD rs1337361092
- S10F (p.Ser10Phe), gnomAD rs1337361092, CADD 19.50, PolyPhen-2 0.41
- S10P (p.Ser10Pro), Ensembl rs1575273361
- S10V (p.Ser10Val), rs1700986801, gnomAD 3-38138722-G-GC, CADD 14.90
- A11G (p.Ala11Gly), ExAC rs777249439, gnomAD rs777249439
- A11T (p.Ala11Thr), rs768025686, ClinGen CA2316016, cosmic curated COSV57181, ClinVar RCV003072566, CADD 9.58, PolyPhen-2 0.00, Uncertain significance, Pyogenic bacterial infections due to MyD88 deficiency
- A11V (p.Ala11Val), ExAC rs777249439, gnomAD rs777249439, CADD 4.16, PolyPhen-2 0.02
- A11E (p.Ala11Glu), rs1365585241, gnomAD 3-38138709-A-AGGA, CADD 22.50
- A11A (p.Ala11Ala), rs1700987447, gnomAD 3-38138733-G-A, CADD 7.01
- A12G (p.Ala12Gly), gnomAD rs1157980099
- A12V (p.Ala12Val), cosmic curated COSV57180, gnomAD rs1157980099, CADD 11.70, PolyPhen-2 0.00
- A12A (p.Ala12Ala), rs79867863, gnomAD 3-38138736-C-G, CADD 7.36
- P13Q (p.Pro13Gln), rs587778545, ClinGen CA160957, ClinVar RCV000121610, ExAC rs587778545, CADD 0.76, PolyPhen-2 0.09, Uncertain significance
- P13R (p.Pro13Arg), rs587778545, ClinGen CA2316019, ClinVar RCV002036815, ExAC rs587778545, CADD 0.99, PolyPhen-2 0.06, Uncertain significance, Pyogenic bacterial infections due to MyD88 deficiency
- P13L (p.Pro13Leu), gnomAD 3-38138738-C-T, CADD 1.25, PolyPhen-2 0.00
- P13P (p.Pro13Pro), rs1292597861, gnomAD 3-38138739-G-C, AlphaMissense 0.28, MetaLR 0.03
- V14A (p.Val14Ala), cosmic curated COSV57182, Ensembl rs2125775276
- V14G (p.Val14Gly), Ensembl rs2125775276
- V14I (p.Val14Ile), Ensembl rs2125775273
- V14L (p.Val14Leu), Ensembl rs2125775273
- V14V (p.Val14Val), rs763301680, gnomAD 3-38138742-C-T, CADD 1.59
- S15C (p.Ser15Cys), ExAC rs771227546, gnomAD rs771227546, CADD 9.72, PolyPhen-2 0.00
- S15F (p.Ser15Phe), ExAC rs771227546, gnomAD rs771227546, CADD 8.88
- S15P (p.Ser15Pro), gnomAD 3-38138743-T-C, AlphaMissense 0.62, MetaLR 0.06
- S15S (p.Ser15Ser), rs1220612814, gnomAD 3-38138745-C-T, CADD 9.67
- S16C (p.Ser16Cys), gnomAD rs1300553231, CADD 13.70, PolyPhen-2 0.00
- S16S (p.Ser16Ser), rs1700988918, gnomAD 3-38138748-C-T, AlphaMissense 0.80, MetaLR 0.13
- T17I (p.Thr17Ile), Ensembl rs2125775310
- p.Thr17 Ser19del, rs1197233489, gnomAD 3-38138742-CTCCTC, CADD 11.00
- T17T (p.Thr17Thr), gnomAD 3-38138751-A-G, CADD 6.42
- S18F (p.Ser18Phe), ESP rs377224266, ExAC rs377224266, gnomAD rs377224266, CADD 11.10, PolyPhen-2 0.00
- S18Y (p.Ser18Tyr), ESP rs377224266, ExAC rs377224266, gnomAD rs377224266
- S18C (p.Ser18Cys), gnomAD 3-38138753-C-G, CADD 13.00, PolyPhen-2 0.11
- S18S (p.Ser18Ser), rs1438800512, gnomAD 3-38138754-C-G, CADD 7.07
- S19C (p.Ser19Cys), ExAC rs759720432, TOPMed rs759720432, gnomAD rs759720432, CADD 22.20, PolyPhen-2 0.34
- S19F (p.Ser19Phe), ExAC rs759720432, TOPMed rs759720432, gnomAD rs759720432, CADD 18.70, PolyPhen-2 0.06
- S19P (p.Ser19Pro), TOPMed rs1290317924
- S19T (p.Ser19Thr), gnomAD 3-38138755-T-A, CADD 14.50, PolyPhen-2 0.03
- S19S (p.Ser19Ser), gnomAD 3-38138757-C-G, CADD 6.11
- L20P (p.Leu20Pro), Ensembl rs201050825
- L20I (p.Leu20Ile), gnomAD 3-38138758-C-A, CADD 1.50, PolyPhen-2 0.01
- P21L (p.Pro21Leu), 1000Genomes rs563686976, ExAC rs563686976, TOPMed rs563686976, gnomAD rs563686976, CADD 23.20, PolyPhen-2 0.54, Uncertain significance
- P21R (p.Pro21Arg), rs563686976, ClinGen CA2316024, ClinVar RCV002049818, 1000Genomes rs563686976, CADD 23.10, PolyPhen-2 0.64, Uncertain significance, Pyogenic bacterial infections due to MyD88 deficiency
- P21S (p.Pro21Ser), gnomAD 3-38138761-C-T, CADD 17.10, PolyPhen-2 0.03
- P21P (p.Pro21Pro), rs531199268, gnomAD 3-38138763-C-G, CADD 4.57
- L22M (p.Leu22Met), Ensembl rs2125775364
- L22W (p.Leu22Trp), gnomAD 3-38138760-TC-T, CADD 23.50
- L22L (p.Leu22Leu), rs2125775364, gnomAD 3-38138764-C-T, CADD 7.13
- A23P (p.Ala23Pro), ExAC rs750178090, gnomAD rs750178090
- A23S (p.Ala23Ser), ExAC rs750178090, gnomAD rs750178090
- A23T (p.Ala23Thr), ExAC rs750178090, gnomAD rs750178090, CADD 10.70, PolyPhen-2 0.00
- A24P (p.Ala24Pro), Ensembl rs2125775382
- A24T (p.Ala24Thr), Ensembl rs2125775382, Uncertain significance, Pyogenic bacterial infections due to MyD88 deficiency
- L25R (p.Leu25Arg), Ensembl rs1559483206
- L25L (p.Leu25Leu), rs1700990709, gnomAD 3-38138775-C-T, CADD 13.20
- N26K (p.Asn26Lys), gnomAD rs1423428080
- N26S (p.Asn26Ser), TOPMed rs1700990813, CADD 23.70, PolyPhen-2 0.95
- N26T (p.Asn26Thr), TOPMed rs1700990813
- N26H (p.Asn26His), gnomAD 3-38138776-A-C, CADD 26.30, PolyPhen-2 0.99
- N26N (p.Asn26Asn), rs1423428080, gnomAD 3-38138778-C-T, CADD 12.70
- M27L (p.Met27Leu), TOPMed rs1700991048, Uncertain significance, Pyogenic bacterial infections due to MyD88 deficiency
- M27T (p.Met27Thr), rs201871349, ClinGen CA160960, cosmic curated COSV57182, ClinVar RCV000121611, CADD 22.50, PolyPhen-2 0.04, Benign
- M27I (p.Met27Ile), gnomAD 3-38138781-G-C, CADD 19.40, PolyPhen-2 0.00
- R28* (p.Arg28Ter), ExAC rs779805093, TOPMed rs779805093, gnomAD rs779805093, CADD 36.00
- R28G (p.Arg28Gly), ExAC rs779805093, TOPMed rs779805093, gnomAD rs779805093, CADD 21.30, PolyPhen-2 0.00
- R28P (p.Arg28Pro), cosmic curated COSV57182, Ensembl rs1700991485
- R28Q (p.Arg28Gln), Ensembl rs1700991485, CADD 23.90, PolyPhen-2 0.02
- R28R (p.Arg28Arg), rs779805093, gnomAD 3-38138782-C-A, CADD 14.70
- V29G (p.Val29Gly), Ensembl rs2125775446
- V29M (p.Val29Met), Ensembl rs2125775444
- R30G (p.Arg30Gly), Ensembl rs2125775450
- R30P (p.Arg30Pro), Ensembl rs2125775458
- R30Q (p.Arg30Gln), Ensembl rs2125775458
- R30W (p.Arg30Trp), cosmic curated COSV57181, Ensembl rs2125775450
- R31C (p.Arg31Cys), Ensembl rs2125775468
- R31H (p.Arg31His), ExAC rs751153924, gnomAD rs751153924, CADD 23.20, PolyPhen-2 0.01
- R31L (p.Arg31Leu), gnomAD 3-38138792-G-T, CADD 23.30, PolyPhen-2 0.39
- R31R (p.Arg31Arg), gnomAD 3-38138793-C-T, CADD 15.50
- R32C (p.Arg32Cys), cosmic curated COSV10589, Ensembl rs2125775473
- R32H (p.Arg32His), Ensembl rs992150018, Uncertain significance, Inborn genetic diseases
- R32L (p.Arg32Leu), Ensembl rs992150018, Uncertain significance
- R32P (p.Arg32Pro), Ensembl rs992150018, Uncertain significance
- R32R (p.Arg32Arg), rs1352479189, gnomAD 3-38138796-C-T, CADD 15.40
- S34A (p.Ser34Ala), Ensembl rs2125775491, Uncertain significance
- S34C (p.Ser34Cys), Ensembl rs1319438, Uncertain significance
- S34Y (p.Ser34Tyr), rs1319438, UniProt VAR 072893, Ensembl rs1319438, AlphaMissense 0.63, MetaLR 0.30, Uncertain significance
- S34P (p.Ser34Pro), gnomAD 3-38138800-T-C, CADD 24.60, PolyPhen-2 0.70
- L35V (p.Leu35Val), Ensembl rs2585635, CADD 24.70, PolyPhen-2 0.98
- L35L (p.Leu35Leu), gnomAD 3-38138805-G-C, CADD 12.70
- F36L (p.Phe36Leu), rs372072898, ClinGen CA2316033, ClinVar RCV000646118, ClinVar RCV004025696, CADD 25.40, PolyPhen-2 0.25, Uncertain significance, Inborn genetic diseases; Pyogenic bacterial infections due to MyD88 deficiency
- F36F (p.Phe36Phe), rs2125775512, gnomAD 3-38138808-C-T, CADD 14.30
- N38K (p.Asn38Lys), TOPMed rs867343970, gnomAD rs867343970, Likely benign
- N38S (p.Asn38Ser), rs748676192, ClinGen CA2316034, ClinVar RCV000792435, ExAC rs748676192, CADD 25.40, PolyPhen-2 0.99, Uncertain significance, Pyogenic bacterial infections due to MyD88 deficiency
- N38T (p.Asn38Thr), ExAC rs748676192, TOPMed rs748676192, gnomAD rs748676192, Uncertain significance
- N38Y (p.Asn38Tyr), Ensembl rs2125775517
- N38N (p.Asn38Asn), rs867343970, gnomAD 3-38138814-C-T, CADD 10.00
- V39L (p.Val39Leu), ExAC rs770387646, TOPMed rs770387646, gnomAD rs770387646, Uncertain significance
- V39M (p.Val39Met), rs770387646, ClinGen CA2316035, cosmic curated COSV57175, ClinVar RCV001961426, CADD 22.90, PolyPhen-2 0.76, Uncertain significance, Pyogenic bacterial infections due to MyD88 deficiency
- V39V (p.Val39Val), gnomAD 3-38138817-G-T, CADD 10.10
- R40G (p.Arg40Gly), ExAC rs778396641, gnomAD rs778396641
- R40L (p.Arg40Leu), ExAC rs749723040, TOPMed rs749723040, gnomAD rs749723040, CADD 22.00, PolyPhen-2 0.39
- R40Q (p.Arg40Gln), ExAC rs749723040, TOPMed rs749723040, gnomAD rs749723040
- R40W (p.Arg40Trp), ExAC rs778396641, gnomAD rs778396641, CADD 24.50, PolyPhen-2 0.87
- R40P (p.Arg40Pro), gnomAD 3-38138819-G-C, CADD 16.90, PolyPhen-2 0.01
- R40R (p.Arg40Arg), rs1365188058, gnomAD 3-38138820-G-A, CADD 9.62
- T41S (p.Thr41Ser), rs587778543, ClinGen CA160951, ClinVar RCV000121608, ClinVar RCV002517600, CADD 8.31, PolyPhen-2 0.01, Uncertain significance
- T41T (p.Thr41Thr), gnomAD 3-38138823-A-G, CADD 9.73
- Q42R (p.Gln42Arg), Ensembl rs2125775556
- V43E (p.Val43Glu), Ensembl rs2125775573
- V43G (p.Val43Gly), Ensembl rs2125775573
- V43L (p.Val43Leu), ExAC rs774701316, gnomAD rs774701316, CADD 23.10, PolyPhen-2 0.02
- A44E (p.Ala44Glu), TOPMed rs1426646083, CADD 26.70, PolyPhen-2 0.91
- A44G (p.Ala44Gly), TOPMed rs1426646083, CADD 24.80, PolyPhen-2 0.08
- A44T (p.Ala44Thr), ExAC rs759610895, gnomAD rs759610895, CADD 28.20, PolyPhen-2 0.70
- A44V (p.Ala44Val), TOPMed rs1426646083, CADD 24.60, PolyPhen-2 0.82
- A44A (p.Ala44Ala), rs948079022, gnomAD 3-38138832-G-A, CADD 10.30
- A45G (p.Ala45Gly), cosmic curated COSV10964, Ensembl rs2125775592, CADD 24.00, PolyPhen-2 0.68
- A45P (p.Ala45Pro), gnomAD rs1243036098
- A45S (p.Ala45Ser), gnomAD rs1243036098, CADD 22.40, PolyPhen-2 0.16
- A45T (p.Ala45Thr), gnomAD rs1243036098
- A45V (p.Ala45Val), Ensembl rs2125775592
- A45A (p.Ala45Ala), rs772208378, gnomAD 3-38138835-C-T, CADD 13.50
- D46G (p.Asp46Gly), gnomAD rs1374235413, CADD 27.40, PolyPhen-2 0.13
- D46H (p.Asp46His), gnomAD rs980606265
- D46N (p.Asp46Asn), gnomAD rs980606265, CADD 25.00, PolyPhen-2 0.44
- W47* (p.Trp47Ter), Ensembl rs2125775607, CADD 32.00
- W47R (p.Trp47Arg), gnomAD 3-38138839-T-C, CADD 32.00, PolyPhen-2 1.00
- T48I (p.Thr48Ile), cosmic curated COSV57179, Ensembl rs2125775612
- T48S (p.Thr48Ser), Ensembl rs2125775610, CADD 14.00, PolyPhen-2 0.02
- T48T (p.Thr48Thr), rs775498014, gnomAD 3-38138844-C-A, CADD 3.36
- A49E (p.Ala49Glu), TOPMed rs1156783898
- A49G (p.Ala49Gly), TOPMed rs1156783898
- A49P (p.Ala49Pro), gnomAD rs1700995743
- A49T (p.Ala49Thr), gnomAD rs1700995743
- A49A (p.Ala49Ala), gnomAD 3-38138847-G-T, CADD 9.74
- A51T (p.Ala51Thr), Ensembl rs2125775632
- A51V (p.Ala51Val), ExAC rs761769496, CADD 27.90, PolyPhen-2 0.98
- A51G (p.Ala51Gly), gnomAD 3-38138852-C-G, CADD 28.50, PolyPhen-2 0.99
- A51A (p.Ala51Ala), rs2125775637, gnomAD 3-38138853-G-A, CADD 8.86
- E52D (p.Glu52Asp), TOPMed rs1417201017, gnomAD rs1417201017, CADD 24.50, PolyPhen-2 0.53, Likely benign, in IMD68
- E52G (p.Glu52Gly), Ensembl rs1575273795
- E52* (p.Glu52Ter), gnomAD 3-38138854-G-T, CADD 37.00
- E52A (p.Glu52Ala), gnomAD 3-38138855-A-C, CADD 28.30, PolyPhen-2 0.99
- E53* (p.Glu53Ter), rs765198848, ClinGen CA352128645, ClinVar RCV001784687, ExAC rs765198848, AlphaMissense 0.17, MetaLR 0.38, Pathogenic
- E53G (p.Glu53Gly), gnomAD rs1337358823, CADD 24.40, PolyPhen-2 0.34
- E53K (p.Glu53Lys), rs765198848, ClinGen CA2316043, ClinVar RCV001990133, ExAC rs765198848, AlphaMissense 0.17, MetaLR 0.38, Uncertain significance, Pyogenic bacterial infections due to MyD88 deficiency
- E53del (p.Glu53del), rs878852993, gnomAD 3-38138852-CGGA-C, CADD 22.50
- E53D (p.Glu53Asp), gnomAD 3-38138859-G-C, CADD 22.80, PolyPhen-2 0.34
- M54I (p.Met54Ile), 1000Genomes rs200093616, CADD 22.60, PolyPhen-2 0.30
- M54V (p.Met54Val), rs750337749, ClinGen CA2316044, cosmic curated COSV57182, ClinVar RCV002833445, AlphaMissense 0.40, MetaLR 0.53, Uncertain significance, Pyogenic bacterial infections due to MyD88 deficiency
- M54K (p.Met54Lys), gnomAD 3-38138861-T-A, CADD 25.30, PolyPhen-2 0.87
Public MYD88 analysis runs
- MYD88 analysis run — MYD88 (1,230 variants) — completed 2026-08-10