MYC (Myc proto-oncogene protein) variants and mutations
MYC (also known as Myc proto-oncogene protein) is a human protein-coding gene encoding a myc proto-oncogene protein. It activates broad transcriptional programs for ribosome production, metabolism, biomass accumulation, and cell-cycle progression. Translocation, amplification, or other persistent activation is a central driver of many cancers, including the hallmark MYC rearrangements of Burkitt lymphoma. This analysis covers 1,872 MYC variants and mutations. Of these, 38% have computational variant effect predictions. Disease context includes Burkitt lymphoma, neurodegenerative disease, and urinary bladder carcinoma. Example MYC variants include D2G, D2H, and D2Y.
Variant analysis overview
- Gene: MYC
- Protein: Myc proto-oncogene protein
- UniProt accession: P01106
- Organism: Homo sapiens
- Variants analyzed: 1872
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 1,661 unspecified-consequence records; 116 missense variants; 52 synonymous variants; 2 in-frame insertions; 22 frameshift variants; 2 in-frame deletions; 8 stop-gained variants; 2 stop lost; 6 substitution
- Prediction scores: 702 variants have prediction scores (38% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Burkitt lymphoma, neurodegenerative disease, urinary bladder carcinoma, urinary bladder cancer, asthma, prostate carcinoma, type 2 diabetes mellitus, diffuse large B-cell lymphoma, diabetes mellitus, lymphoma, clear cell renal carcinoma, allergic rhinitis.
Protein structure and variant hotspots
- Protein features: 1 domains; 24 post-translational modification sites.
- Structural context: 220 variants have structural context.
- PTM context: 98 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 MYC variants
Examples include D2G, D2H, D2Y, F3L, R5G, R5L, R5P, R5Q. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- D2G (p.Asp2Gly), cosmic curated COSV52377, Ensembl rs1586587947, CADD 27.40, PolyPhen-2 0.06
- D2H (p.Asp2His), cosmic curated COSV10438, ExAC rs778595707, TOPMed rs778595707, gnomAD rs778595707
- D2Y (p.Asp2Tyr), cosmic curated COSV10500, ExAC rs778595707, TOPMed rs778595707, gnomAD rs778595707, CADD 31.00, PolyPhen-2 0.65
- F3L (p.Phe3Leu), ExAC rs772459508, gnomAD rs772459508, CADD 18.20, PolyPhen-2 0.00
- R5G (p.Arg5Gly), Ensembl rs2130084102
- R5L (p.Arg5Leu), ExAC rs747141352, TOPMed rs747141352, gnomAD rs747141352
- R5P (p.Arg5Pro), ExAC rs747141352, TOPMed rs747141352, gnomAD rs747141352, CADD 20.20
- R5Q (p.Arg5Gln), cosmic curated COSV52368, ExAC rs747141352, TOPMed rs747141352, gnomAD rs747141352, CADD 22.30, PolyPhen-2 0.00
- R5W (p.Arg5Trp), Ensembl rs2130084102
- R5C (p.Arg5Cys), gnomAD 8-127735476-C-T, CADD 13.70
- R5S (p.Arg5Ser), gnomAD 8-127735476-C-A, CADD 13.30
- R5H (p.Arg5His), rs773815056, gnomAD 8-127735477-G-A, CADD 15.70
- R5R (p.Arg5Arg), gnomAD 8-127735478-T-C, CADD 15.10
- R5* (p.Arg5Ter), gnomAD 8-127736049-C-T, CADD 7.51
- R5M (p.Arg5Met), gnomAD 8-127736068-G-T, CADD 14.10, SIFT 0.00
- V6I (p.Val6Ile), cosmic curated COSV10500, ExAC rs777141161, gnomAD rs777141161, CADD 2.46, PolyPhen-2 0.00
- V6A (p.Val6Ala), gnomAD 8-127735486-T-C, CADD 10.60
- V6V (p.Val6Val), gnomAD 8-127735487-T-C, CADD 15.80
- V7A (p.Val7Ala), cosmic curated COSV10438, Ensembl rs2130084159
- V7L (p.Val7Leu), cosmic curated COSV52382, Ensembl rs2130084153
- V7M (p.Val7Met), cosmic curated COSV52367, Ensembl rs2130084153
- V7I (p.Val7Ile), rs1813565628, gnomAD 8-127735509-G-A, CADD 1.46
- V7V (p.Val7Val), gnomAD 8-127735511-T-G, CADD 4.85
- E8G (p.Glu8Gly), cosmic curated COSV52376, ExAC rs759986640, gnomAD rs759986640, CADD 22.00, PolyPhen-2 0.00
- E8S (p.Glu8Ser), gnomAD 8-127736070-AC-A, CADD 15.00
- E8R (p.Glu8Arg), gnomAD 8-127736070-A-AC, CADD 16.20
- E8* (p.Glu8Ter), rs1490830929, gnomAD 8-127736076-G-T, CADD 9.37
- E8D (p.Glu8Asp), gnomAD 8-127736078-G-T, CADD 17.20, SIFT 0.00
- N9I (p.Asn9Ile), TOPMed rs1381903406, gnomAD rs1381903406, CADD 12.20, PolyPhen-2 0.00
- N9K (p.Asn9Lys), cosmic curated COSV52370, Ensembl rs2130084186
- Q10H (p.Gln10His), TOPMed rs1319018025, gnomAD rs1319018025, CADD 28.40, PolyPhen-2 0.06
- Q11* (p.Gln11Ter), cosmic curated COSV10878, TOPMed rs1813639473, CADD 38.00
- Q11H (p.Gln11His), ExAC rs781165176, gnomAD rs781165176
- P12H (p.Pro12His), ESP rs139294902, ExAC rs139294902, TOPMed rs139294902, gnomAD rs139294902
- P12R (p.Pro12Arg), ESP rs139294902, ExAC rs139294902, TOPMed rs139294902, gnomAD rs139294902, CADD 21.70, PolyPhen-2 0.03
- P12T (p.Pro12Thr), cosmic curated COSV10501, Ensembl rs2130092034
- P12P (p.Pro12Pro), gnomAD 8-127736075-C-A, CADD 6.21
- P13L (p.Pro13Leu), Ensembl rs2130092076
- A14E (p.Ala14Glu), Ensembl rs2130092100
- A14G (p.Ala14Gly), Ensembl rs2130092100
- A14P (p.Ala14Pro), ExAC rs770253839, TOPMed rs770253839, gnomAD rs770253839, CADD 18.30, PolyPhen-2 0.24
- A14T (p.Ala14Thr), cosmic curated COSV10501, ExAC rs770253839, TOPMed rs770253839, gnomAD rs770253839, CADD 14.90, PolyPhen-2 0.00
- A14S (p.Ala14Ser), gnomAD 8-127735572-G-T, CADD 4.38
- A14A (p.Ala14Ala), rs1335036147, gnomAD 8-127735574-G-A, CADD 9.23
- A14V (p.Ala14Val), gnomAD 8-127736152-C-T, CADD 19.30, SIFT 0.03
- A14D (p.Ala14Asp), gnomAD 8-127736152-C-A, CADD 18.70, SIFT 0.02
- T15K (p.Thr15Lys), ExAC rs775909833, TOPMed rs775909833, gnomAD rs775909833, CADD 23.20, PolyPhen-2 0.00
- T15M (p.Thr15Met), ExAC rs775909833, TOPMed rs775909833, gnomAD rs775909833
- T15P (p.Thr15Pro), Ensembl rs2130092121
- T15S (p.Thr15Ser), Ensembl rs2130092121
- T15I (p.Thr15Ile), rs1030529319, gnomAD 8-127736071-C-T, CADD 16.60, SIFT 0.00
- T15N (p.Thr15Asn), rs1030529319, gnomAD 8-127736071-C-A, CADD 16.20, SIFT 0.00
- T15T (p.Thr15Thr), gnomAD 8-127736072-C-A, CADD 16.70
- M16I (p.Met16Ile), Ensembl rs2130092144
- M16L (p.Met16Leu), rs1813565973, gnomAD 8-127735521-A-T, CADD 4.58
- M16T (p.Met16Thr), rs954155900, gnomAD 8-127735522-T-C, CADD 8.60
- P17S (p.Pro17Ser), cosmic curated COSV52373, TOPMed rs1382266165, gnomAD rs1382266165, CADD 12.70
- P17T (p.Pro17Thr), cosmic curated COSV10500, TOPMed rs1382266165, gnomAD rs1382266165, CADD 26.70, PolyPhen-2 0.97
- P17I (p.Pro17Ile), gnomAD 8-127735523-GCCTC, CADD 9.23
- P17L (p.Pro17Leu), rs1184326185, gnomAD 8-127735525-C-T, CADD 11.10
- P17H (p.Pro17His), gnomAD 8-127735525-C-A, CADD 10.40
- P17P (p.Pro17Pro), gnomAD 8-127735526-T-C, CADD 9.88
- P17R (p.Pro17Arg), rs546283688, gnomAD 8-127735540-C-G, CADD 7.21
- P17Q (p.Pro17Gln), rs1027454697, gnomAD 8-127736095-C-A, CADD 3.26, SIFT 0.31
- P17A (p.Pro17Ala), gnomAD 8-127736109-C-G, CADD 10.20, SIFT 1.00
- L18F (p.Leu18Phe), cosmic curated COSV10438, Ensembl rs1813639928, CADD 23.70, PolyPhen-2 0.98
- L18I (p.Leu18Ile), Ensembl rs1813639928
- L18* (p.Leu18Ter), gnomAD 8-127735488-AT-A, CADD 14.50
- L18P (p.Leu18Pro), rs1813565243, gnomAD 8-127735501-T-C, CADD 11.80
- L18L (p.Leu18Leu), gnomAD 8-127735502-A-G, CADD 8.26
- L18Y (p.Leu18Tyr), gnomAD 8-127735516-TCC-T, CADD 8.71
- L18R (p.Leu18Arg), rs1813565868, gnomAD 8-127735519-T-G, CADD 5.67
- p.Leu16dup, gnomAD 8-127735520-T-TTT, CADD 2.14
- L18V (p.Leu18Val), rs1446473214, gnomAD 8-127735527-C-G, CADD 6.92
- L18Q (p.Leu18Gln), rs1813581014, gnomAD 8-127736065-T-A, CADD 1.04, SIFT 0.42
- L18M (p.Leu18Met), rs1813581427, gnomAD 8-127736079-C-A, CADD 16.30, SIFT 0.20
- N19K (p.Asn19Lys), 1000Genomes rs149992096, ESP rs149992096, ExAC rs149992096, TOPMed rs149992096, CADD 23.60, PolyPhen-2 0.19
- V20I (p.Val20Ile), cosmic curated COSV52367, Ensembl rs1813640119
- V20L (p.Val20Leu), cosmic curated COSV10501, Ensembl rs1813640119
- S21R (p.Ser21Arg), cosmic curated COSV52367, ExAC rs772792914, TOPMed rs772792914, NCI-TCGA Cosmic COSV5236, Variant assessed as somatic; moderate impact.
- S21P (p.Ser21Pro), gnomAD 8-127735530-T-C, CADD 4.78
- S21Y (p.Ser21Tyr), gnomAD 8-127735530-T-TAC, CADD 6.93
- S21L (p.Ser21Leu), rs1813580472, gnomAD 8-127736051-AG-A, CADD 14.40
- S21T (p.Ser21Thr), gnomAD 8-127736055-T-A, CADD 14.30, SIFT 0.00
- S21F (p.Ser21Phe), gnomAD 8-127736056-C-T, CADD 14.90, SIFT 0.00
- S21C (p.Ser21Cys), rs1813580580, gnomAD 8-127736056-C-G, CADD 14.60, SIFT 0.00
- S21S (p.Ser21Ser), rs1813580621, gnomAD 8-127736057-T-G, CADD 7.27
- S21W (p.Ser21Trp), gnomAD 8-127736089-C-G, CADD 9.18, SIFT 0.00
- S21* (p.Ser21Ter), gnomAD 8-127736089-C-A, CADD 9.06
- F22I (p.Phe22Ile), cosmic curated COSV10438, 1000Genomes rs146505192, ESP rs146505192, ExAC rs146505192, Benign
- F22L (p.Phe22Leu), rs146505192, ClinGen CA4875217, cosmic curated COSV52370, ClinVar RCV000896531, CADD 18.80, PolyPhen-2 0.01, Benign/Likely benign, not provided
- F22V (p.Phe22Val), 1000Genomes rs146505192, ESP rs146505192, ExAC rs146505192, TOPMed rs146505192, CADD 22.70, PolyPhen-2 0.13, Benign
- F22S (p.Phe22Ser), gnomAD 8-127735509-GT-G, CADD 9.03
- p.Phe21 Leu22del, gnomAD 8-127735532-ATTCC, CADD 4.00
- T23S (p.Thr23Ser), rs867382866, gnomAD 8-127735549-C-G, CADD 8.65
- T23I (p.Thr23Ile), gnomAD 8-127735549-C-T, CADD 9.04
- T23T (p.Thr23Thr), gnomAD 8-127735550-T-C, CADD 5.35
- T23N (p.Thr23Asn), gnomAD 8-127735583-T-TA, CADD 3.67
- N24K (p.Asn24Lys), Ensembl rs2130092271, CADD 22.70, PolyPhen-2 0.16
- N24S (p.Asn24Ser), cosmic curated COSV52375, ESP rs148915481, ExAC rs148915481, TOPMed rs148915481, CADD 12.00, PolyPhen-2 0.01
- N24Y (p.Asn24Tyr), gnomAD rs1490644442, CADD 24.10, PolyPhen-2 0.80
- R25G (p.Arg25Gly), cosmic curated COSV99422, Ensembl rs2130092281, CADD 28.80, PolyPhen-2 0.01
- R25S (p.Arg25Ser), cosmic curated COSV10501, TOPMed rs1813640492
- R25T (p.Arg25Thr), Ensembl rs2130092289
- R25C (p.Arg25Cys), gnomAD 8-127735560-C-T, CADD 11.20
- R25P (p.Arg25Pro), gnomAD 8-127735561-G-C, CADD 3.09
- R25H (p.Arg25His), gnomAD 8-127735561-G-A, CADD 3.52
- R25L (p.Arg25Leu), gnomAD 8-127735570-G-T, CADD 9.28
- R25R (p.Arg25Arg), rs972783453, gnomAD 8-127735571-C-A, CADD 9.72
- R25W (p.Arg25Trp), rs1273978636, gnomAD 8-127736091-C-T, CADD 12.70, SIFT 0.03
- R25Q (p.Arg25Gln), gnomAD 8-127736092-G-A, CADD 2.10, SIFT 0.35
- R25I (p.Arg25Ile), gnomAD 8-127736180-CGGAG, CADD 18.60
- R25M (p.Arg25Met), gnomAD 8-127736188-G-T, CADD 16.00, SIFT 0.02
- N26S (p.Asn26Ser), rs4645959, ClinGen CA4875220, cosmic curated COSV52371, ClinVar RCV002227948, CADD 26.70, PolyPhen-2 0.16, Uncertain significance, not provided; Classic Hodgkin lymphoma
- N26T (p.Asn26Thr), 1000Genomes rs4645959, ESP rs4645959, ExAC rs4645959, TOPMed rs4645959, CADD 28.10, PolyPhen-2 0.01, Benign
- N26D (p.Asn26Asp), gnomAD 8-127735551-A-G, CADD 3.96
- Y27N (p.Tyr27Asn), cosmic curated COSV52372, gnomAD rs1418866533, CADD 25.70, PolyPhen-2 0.95
- Y27S (p.Tyr27Ser), gnomAD 8-127735540-C-CGA, CADD 5.70
- Y27Y (p.Tyr27Tyr), gnomAD 8-127735547-C-T, CADD 7.34
- D28A (p.Asp28Ala), gnomAD rs1183060749
- D28H (p.Asp28His), Ensembl rs2130092355
- D28V (p.Asp28Val), gnomAD rs1183060749, CADD 32.00, PolyPhen-2 1.00
- L29I (p.Leu29Ile), ESP rs375812644, ExAC rs375812644, TOPMed rs375812644, gnomAD rs375812644
- L29V (p.Leu29Val), cosmic curated COSV52380, ESP rs375812644, ExAC rs375812644, TOPMed rs375812644
- L29F (p.Leu29Phe), rs924272872, gnomAD 8-127735587-C-T, CADD 10.40
- L29P (p.Leu29Pro), rs1813567766, gnomAD 8-127735591-T-C, CADD 5.66
- L29L (p.Leu29Leu), gnomAD 8-127736126-C-G, CADD 9.25
- L29H (p.Leu29His), gnomAD 8-127736164-T-A, CADD 21.60, SIFT 0.04
- D30E (p.Asp30Glu), Ensembl rs2130092399
- D30H (p.Asp30His), TOPMed rs1813641041
- D30N (p.Asp30Asn), TOPMed rs1813641041
- Y31* (p.Tyr31Ter), Ensembl rs2130092411
- Y31C (p.Tyr31Cys), ExAC rs764006760, gnomAD rs764006760, CADD 31.00, PolyPhen-2 0.99
- Y31F (p.Tyr31Phe), ExAC rs764006760, gnomAD rs764006760
- D32H (p.Asp32His), Ensembl rs2130092421
- S33* (p.Ser33Ter), Ensembl rs776780683
- S33L (p.Ser33Leu), rs776780683, NCI-TCGA Cosmic COSV5237, cosmic curated COSV52377, Ensembl rs776780683, MetaLR 0.20, MetaSVM -0.71, Variant assessed as somatic; moderate impact.
- S33Y (p.Ser33Tyr), gnomAD 8-127735564-C-A, CADD 11.90
- S33C (p.Ser33Cys), gnomAD 8-127735592-T-TTC, CADD 5.39
- S33F (p.Ser33Phe), gnomAD 8-127735594-C-T, CADD 1.62
- S33S (p.Ser33Ser), rs1385341422, gnomAD 8-127735595-C-T, CADD 9.66
- S33P (p.Ser33Pro), gnomAD 8-127735596-T-C, CADD 5.50
- V34M (p.Val34Met), cosmic curated COSV10501, ExAC rs781313941, gnomAD rs781313941, CADD 21.60, PolyPhen-2 0.29
- Q35* (p.Gln35Ter), NCI-TCGA Cosmic COSV9942, cosmic curated COSV99420, Ensembl rs2130092460, Variant assessed as somatic; high impact.
- Q35L (p.Gln35Leu), Ensembl rs2130092470
- Q35E (p.Gln35Glu), gnomAD 8-127736157-C-G, CADD 12.70, SIFT 0.35
- Q35K (p.Gln35Lys), gnomAD 8-127736157-C-A, CADD 12.50, SIFT 1.00
- Q35R (p.Gln35Arg), gnomAD 8-127736158-A-G, CADD 2.33, SIFT 0.77
- P36L (p.Pro36Leu), Ensembl rs2130092481, CADD 28.50, PolyPhen-2 1.00
- P36Q (p.Pro36Gln), Ensembl rs2130092481
- P36T (p.Pro36Thr), gnomAD 8-127735557-C-A, CADD 8.23
- P36P (p.Pro36Pro), gnomAD 8-127735559-A-G, CADD 4.35
- P36S (p.Pro36Ser), gnomAD 8-127735575-C-T, CADD 12.20
- P36H (p.Pro36His), gnomAD 8-127735576-C-A, CADD 4.02
- Y37N (p.Tyr37Asn), Ensembl rs2130092494
- Y39* (p.Tyr39Ter), Ensembl rs2130092523
- Y39F (p.Tyr39Phe), cosmic curated COSV10501, Ensembl rs2130092516
- Y39N (p.Tyr39Asn), Ensembl rs2130092511
- C40* (p.Cys40Ter), Ensembl rs2130092540
- C40W (p.Cys40Trp), cosmic curated COSV52372, Ensembl rs2130092540
- C40Y (p.Cys40Tyr), cosmic curated COSV99420, Ensembl rs2130092534
- p.Cys3dup, gnomAD 8-127735478-T-TTG, CADD 13.40
- C40F (p.Cys40Phe), gnomAD 8-127735480-G-T, CADD 19.90
- C40C (p.Cys40Cys), rs763409129, gnomAD 8-127735481-C-T, CADD 20.10
- C40R (p.Cys40Arg), rs111915501, gnomAD 8-127736082-T-C, CADD 13.70, SIFT 0.52
- C40G (p.Cys40Gly), gnomAD 8-127736082-T-G, CADD 13.50, SIFT 0.49
- C40S (p.Cys40Ser), rs1813581663, gnomAD 8-127736085-T-A, CADD 9.21, SIFT 0.68
- D41E (p.Asp41Glu), Ensembl rs1563757581, CADD 22.80, PolyPhen-2 0.01
- D41G (p.Asp41Gly), gnomAD rs1395774855, CADD 32.00, PolyPhen-2 0.48
- D41H (p.Asp41His), Ensembl rs2130092552
- D41N (p.Asp41Asn), cosmic curated COSV52375, Ensembl rs2130092552, CADD 31.00, PolyPhen-2 0.50
- D41V (p.Asp41Val), gnomAD rs1395774855, CADD 31.00, PolyPhen-2 0.48
- D41Y (p.Asp41Tyr), gnomAD 8-127735617-G-T, CADD 7.23
- D41D (p.Asp41Asp), gnomAD 8-127736192-T-C, CADD 10.00
- E42K (p.Glu42Lys), Ensembl rs2130092577
- E42Q (p.Glu42Gln), Ensembl rs2130092577
- E42V (p.Glu42Val), Ensembl rs2130092603, CADD 31.00, PolyPhen-2 0.50
- E42* (p.Glu42Ter), gnomAD 8-127735566-G-T, CADD 4.57
- E42D (p.Glu42Asp), gnomAD 8-127736141-G-T, CADD 13.20, SIFT 0.09
- E43* (p.Glu43Ter), Ensembl rs2130092622
Public MYC analysis runs
- MYC analysis run — MYC (1,872 variants) — completed 2026-08-18