PML (Protein PML) variants and mutations
PML (also known as Protein PML) is a human protein-coding gene encoding a protein. It organizes PML nuclear bodies that regulate transcription, DNA-damage responses, senescence, apoptosis, and antiviral defense. Fusion of PML with RARA blocks myeloid differentiation in acute promyelocytic leukemia and creates a disease that is highly responsive to differentiation and arsenic-based therapy. This analysis covers 1,384 PML variants and mutations. Of these, 80% have computational variant effect predictions. Disease context includes thyroid gland carcinoma, uterine corpus leiomyoma, and viral infectious disease. Example PML variants include E2K, E2*, and E2D.
Variant analysis overview
- Gene: PML
- Protein: Protein PML
- UniProt accession: P29590
- Organism: Homo sapiens
- Variants analyzed: 1384
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 1,041 unspecified-consequence records; 174 missense variants; 16 stop-gained variants; 132 synonymous variants; 11 frameshift variants; 7 in-frame deletions; 2 in-frame insertions; 1 splice-region variants; 1 substitution
- Prediction scores: 1,108 variants have prediction scores (80% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: thyroid gland carcinoma, uterine corpus leiomyoma, viral infectious disease, type 2 diabetes mellitus, acute myeloid leukemia, diabetes mellitus, skin basal cell carcinoma, carcinoma of liver and intrahepatic biliary tract, colorectal adenocarcinoma, dengue disease, bone Paget disease, hyperlipidemia.
Protein structure and variant hotspots
- Protein features: 16 binding sites; 21 post-translational modification sites.
- PTM context: 34 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 PML variants
Examples include E2K, E2*, E2D, E2E, P3T, P3S, P3H, P3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2K (p.Glu2Lys), gnomAD 15-73994816-G-A, REVEL 0.11, CADD 22.50
- E2* (p.Glu2Ter), gnomAD 15-73994816-G-T, CADD 35.00
- E2D (p.Glu2Asp), gnomAD 15-73994818-G-C, REVEL 0.02, CADD 6.30
- E2E (p.Glu2Glu), rs1388157744, gnomAD 15-73994818-G-A, CADD 4.94
- P3T (p.Pro3Thr), Ensembl rs925273078, REVEL 0.09, CADD 22.60
- P3S (p.Pro3Ser), gnomAD 15-73994819-C-T, REVEL 0.10, CADD 22.70
- P3H (p.Pro3His), gnomAD 15-73994820-C-A, REVEL 0.12, CADD 23.80
- P3L (p.Pro3Leu), gnomAD 15-73994820-C-T, REVEL 0.09, CADD 24.10
- P3P (p.Pro3Pro), gnomAD 15-73994821-T-G, CADD 4.72
- A4T (p.Ala4Thr), gnomAD rs1450586395, REVEL 0.08, CADD 20.40
- A4V (p.Ala4Val), gnomAD rs1225562023, REVEL 0.04, CADD 13.90
- A4S (p.Ala4Ser), gnomAD 15-73994822-G-T, REVEL 0.10, CADD 18.40
- A4E (p.Ala4Glu), gnomAD 15-73994823-C-A, REVEL 0.04, CADD 12.30
- P5A (p.Pro5Ala), gnomAD rs1257467598, REVEL 0.04, CADD 6.38
- P5H (p.Pro5His), Ensembl rs975151127, REVEL 0.06, CADD 22.30
- P5S (p.Pro5Ser), gnomAD 15-73994825-C-T, REVEL 0.03, CADD 8.19
- P5T (p.Pro5Thr), gnomAD 15-73994825-C-A, REVEL 0.04, CADD 8.05
- P5L (p.Pro5Leu), gnomAD 15-73994826-C-T, REVEL 0.05, CADD 18.80
- P5P (p.Pro5Pro), gnomAD 15-73994827-C-G, CADD 5.70
- A6T (p.Ala6Thr), gnomAD 15-73994828-G-A, REVEL 0.03, CADD 5.77
- A6S (p.Ala6Ser), gnomAD 15-73994828-G-T, REVEL 0.01, CADD 3.53
- A6V (p.Ala6Val), gnomAD 15-73994829-C-T, REVEL 0.11, CADD 13.10
- A6D (p.Ala6Asp), gnomAD 15-73994829-C-A, REVEL 0.10, CADD 16.90
- A6A (p.Ala6Ala), rs1204201542, gnomAD 15-73994830-C-T, CADD 7.12
- R7* (p.Arg7Ter), NCI-TCGA TCGA novel, CADD 22.90, Variant assessed as somatic; high impact.
- R7L (p.Arg7Leu), rs1482238182, ClinGen CA393114917, ClinVar RCV004130956, TOPMed rs1482238182, REVEL 0.08, CADD 19.50, Uncertain significance, not specified
- R7R (p.Arg7Arg), rs574579963, gnomAD 15-73994831-C-A, CADD 1.25
- R7G (p.Arg7Gly), gnomAD 15-73994831-C-G, REVEL 0.00, CADD 0.05
- R7Q (p.Arg7Gln), gnomAD 15-73994832-G-A, REVEL 0.10, CADD 19.20
- S8F (p.Ser8Phe), 1000Genomes rs542097036, ExAC rs542097036, gnomAD rs542097036, REVEL 0.14, CADD 23.00
- S8Y (p.Ser8Tyr), 1000Genomes rs542097036, ExAC rs542097036, gnomAD rs542097036, REVEL 0.15, CADD 22.70
- S8P (p.Ser8Pro), gnomAD 15-73994834-T-C, REVEL 0.05, CADD 22.50
- S8S (p.Ser8Ser), gnomAD 15-73994836-T-G, CADD 7.22
- P9A (p.Pro9Ala), TOPMed rs1479031859
- P9L (p.Pro9Leu), gnomAD rs1429883570, REVEL 0.02, CADD 13.60
- P9T (p.Pro9Thr), gnomAD 15-73994837-C-A, REVEL 0.04, CADD 3.53
- P9S (p.Pro9Ser), gnomAD 15-73994837-C-T, REVEL 0.02, CADD 1.67
- P9Q (p.Pro9Gln), gnomAD 15-73994838-C-A, REVEL 0.06, CADD 21.20
- P9R (p.Pro9Arg), gnomAD 15-73994838-C-G, REVEL 0.05, CADD 21.10
- P9P (p.Pro9Pro), gnomAD 15-73994839-G-T, CADD 4.46
- R10K (p.Arg10Lys), gnomAD rs1168158486, REVEL 0.05, CADD 13.90
- R10M (p.Arg10Met), gnomAD rs1168158486, REVEL 0.05, CADD 15.00
- R10G (p.Arg10Gly), gnomAD 15-73994840-A-G, REVEL 0.04, CADD 5.07
- R10S (p.Arg10Ser), gnomAD 15-73994842-G-T, REVEL 0.05, CADD 10.40
- R10R (p.Arg10Arg), rs763855768, gnomAD 15-73994842-G-A, CADD 7.46
- P11S (p.Pro11Ser), TOPMed rs1469928575, gnomAD rs1469928575, REVEL 0.07, CADD 8.54
- P11T (p.Pro11Thr), gnomAD 15-73994843-C-A, REVEL 0.09, CADD 7.42
- P11H (p.Pro11His), gnomAD 15-73994844-C-A, REVEL 0.06, CADD 19.20
- P11R (p.Pro11Arg), gnomAD 15-73994844-C-G, REVEL 0.06, CADD 9.69
- P11L (p.Pro11Leu), gnomAD 15-73994844-C-T, REVEL 0.09, CADD 10.10
- P11P (p.Pro11Pro), rs1450029541, gnomAD 15-73994845-C-T, CADD 5.90
- Q12* (p.Gln12Ter), NCI-TCGA TCGA novel, CADD 33.00, Variant assessed as somatic; high impact.
- Q12K (p.Gln12Lys), gnomAD 15-73994846-C-A, REVEL 0.05, CADD 11.50
- Q12R (p.Gln12Arg), gnomAD 15-73994847-A-G, REVEL 0.09, CADD 14.00
- Q12Q (p.Gln12Gln), gnomAD 15-73994848-G-A, CADD 4.55
- Q12H (p.Gln12His), gnomAD 15-73994848-G-T, REVEL 0.05, CADD 18.30
- Q13E (p.Gln13Glu), TOPMed rs1277045101, gnomAD rs1277045101, REVEL 0.06, CADD 13.20
- Q13* (p.Gln13Ter), gnomAD 15-73994849-C-T, CADD 33.00
- Q13K (p.Gln13Lys), gnomAD 15-73994849-C-A, REVEL 0.04, CADD 9.79
- Q13R (p.Gln13Arg), gnomAD 15-73994850-A-G, REVEL 0.04, CADD 6.58
- Q13Q (p.Gln13Gln), rs1177974439, gnomAD 15-73994851-G-A, CADD 3.72
- Q13H (p.Gln13His), gnomAD 15-73994851-G-T, REVEL 0.04, CADD 14.00
- D14A (p.Asp14Ala), Ensembl rs2141690668
- D14N (p.Asp14Asn), gnomAD 15-73994852-G-A, REVEL 0.03, CADD 9.71
- D14Y (p.Asp14Tyr), gnomAD 15-73994852-G-T, REVEL 0.10, CADD 19.70
- D14G (p.Asp14Gly), gnomAD 15-73994853-A-G, REVEL 0.15, CADD 14.20
- D14E (p.Asp14Glu), gnomAD 15-73994854-C-A, REVEL 0.08, CADD 5.99
- D14D (p.Asp14Asp), gnomAD 15-73994854-C-T, CADD 3.13
- P15A (p.Pro15Ala), TOPMed rs1020660622, REVEL 0.03, CADD 0.04
- P15S (p.Pro15Ser), TOPMed rs1020660622, REVEL 0.02, CADD 0.03
- P15T (p.Pro15Thr), gnomAD 15-73994855-C-A, REVEL 0.04, CADD 0.69
- P15L (p.Pro15Leu), gnomAD 15-73994856-C-T, REVEL 0.04, CADD 12.10
- P15H (p.Pro15His), gnomAD 15-73994856-C-A, REVEL 0.06, CADD 15.80
- P15P (p.Pro15Pro), rs1047555898, gnomAD 15-73994857-C-A, CADD 3.65
- A16P (p.Ala16Pro), Ensembl rs886298849, REVEL 0.07, CADD 20.60
- A16T (p.Ala16Thr), cosmic curated COSV10635, Ensembl rs886298849, REVEL 0.04, CADD 11.20
- A16R (p.Ala16Arg), rs2141690677, gnomAD 15-73994853-A-AC, CADD 18.80
- A16S (p.Ala16Ser), gnomAD 15-73994858-G-T, REVEL 0.05, CADD 14.00
- A16G (p.Ala16Gly), gnomAD 15-73994859-C-G, REVEL 0.01, CADD 5.76
- A16D (p.Ala16Asp), gnomAD 15-73994859-C-A, REVEL 0.06, CADD 12.70
- A16V (p.Ala16Val), gnomAD 15-73994859-C-T, REVEL 0.01, CADD 5.77
- A16A (p.Ala16Ala), gnomAD 15-73994860-C-T, CADD 7.88
- R17G (p.Arg17Gly), ExAC rs751354376, TOPMed rs751354376, gnomAD rs751354376
- R17P (p.Arg17Pro), Ensembl rs2141690755, REVEL 0.03, CADD 3.99
- R17W (p.Arg17Trp), NCI-TCGA Cosmic COSV5144, cosmic curated COSV51445, REVEL 0.13, CADD 18.50, Variant assessed as somatic; moderate impact.
- R17R (p.Arg17Arg), rs751354376, gnomAD 15-73994861-C-A, CADD 7.21
- R17L (p.Arg17Leu), gnomAD 15-73994862-G-T, REVEL 0.01, CADD 0.19
- R17Q (p.Arg17Gln), gnomAD 15-73994862-G-A, REVEL 0.03, CADD 3.73
- P18S (p.Pro18Ser), TOPMed rs2069392096, REVEL 0.01, CADD 5.97
- P18T (p.Pro18Thr), gnomAD 15-73994864-C-A, REVEL 0.01, CADD 4.18
- P18R (p.Pro18Arg), gnomAD 15-73994865-C-G, REVEL 0.02, CADD 13.10
- P18H (p.Pro18His), gnomAD 15-73994865-C-A, REVEL 0.05, CADD 17.00
- P18P (p.Pro18Pro), gnomAD 15-73994866-C-T, CADD 7.05
- Q19H (p.Gln19His), Ensembl rs2141690801, REVEL 0.03, CADD 0.08
- Q19P (p.Gln19Pro), cosmic curated COSV10586, Ensembl rs2141690794, REVEL 0.02, CADD 0.15
- Q19K (p.Gln19Lys), gnomAD 15-73994867-C-A, REVEL 0.10, CADD 1.41
- Q19* (p.Gln19Ter), gnomAD 15-73994867-C-T, CADD 28.70
- Q19R (p.Gln19Arg), gnomAD 15-73994868-A-G, REVEL 0.02, CADD 0.05
- Q19Q (p.Gln19Gln), gnomAD 15-73994869-G-A, CADD 1.94
- E20A (p.Glu20Ala), Ensembl rs2141690825, REVEL 0.06, CADD 4.13
- E20D (p.Glu20Asp), TOPMed rs1273074911, REVEL 0.02, CADD 7.32
- E20G (p.Glu20Gly), Ensembl rs2141690825, REVEL 0.03, CADD 10.40
- E20Q (p.Glu20Gln), Ensembl rs2141690814
- E20* (p.Glu20Ter), gnomAD 15-73994870-G-T, CADD 24.60
- E20K (p.Glu20Lys), gnomAD 15-73994870-G-A, REVEL 0.01, CADD 1.16
- E20V (p.Glu20Val), gnomAD 15-73994871-A-T, REVEL 0.03, CADD 14.70
- E20E (p.Glu20Glu), gnomAD 15-73994872-G-A, CADD 4.59
- P21R (p.Pro21Arg), TOPMed rs2069392568, REVEL 0.09, CADD 22.90
- P21S (p.Pro21Ser), gnomAD rs1466002928, REVEL 0.02, CADD 12.60
- P21T (p.Pro21Thr), gnomAD 15-73994873-C-A, REVEL 0.03, CADD 16.20
- P21A (p.Pro21Ala), gnomAD 15-73994873-C-G, REVEL 0.02, CADD 15.30
- P21L (p.Pro21Leu), gnomAD 15-73994874-C-T, REVEL 0.11, CADD 21.50
- P21H (p.Pro21His), gnomAD 15-73994874-C-A, REVEL 0.09, CADD 23.00
- P21P (p.Pro21Pro), gnomAD 15-73994875-C-A, CADD 11.30
- T22P (p.Thr22Pro), Ensembl rs2141690893, REVEL 0.05, CADD 22.40
- T22I (p.Thr22Ile), gnomAD 15-73994877-C-T, REVEL 0.06, CADD 22.70
- T22N (p.Thr22Asn), gnomAD 15-73994877-C-A, REVEL 0.06, CADD 18.70
- T22T (p.Thr22Thr), gnomAD 15-73994878-C-T, CADD 11.00
- M23I (p.Met23Ile), gnomAD rs1380719368, REVEL 0.14, CADD 23.60
- M23L (p.Met23Leu), gnomAD rs1364577658, REVEL 0.10, CADD 23.30
- M23R (p.Met23Arg), Ensembl rs2141690911
- M23V (p.Met23Val), gnomAD rs1364577658, REVEL 0.14, CADD 21.40
- M23T (p.Met23Thr), gnomAD 15-73994880-T-C, REVEL 0.12, CADD 21.90
- M23K (p.Met23Lys), gnomAD 15-73994880-T-A, REVEL 0.15, CADD 23.40
- P24L (p.Pro24Leu), Ensembl rs1595870267
- P24S (p.Pro24Ser), TOPMed rs1274872826, gnomAD rs1274872826, REVEL 0.06, CADD 15.20
- P24T (p.Pro24Thr), gnomAD 15-73994882-C-A, REVEL 0.05, CADD 17.20
- P24H (p.Pro24His), gnomAD 15-73994883-C-A, REVEL 0.09, CADD 24.20
- P24P (p.Pro24Pro), gnomAD 15-73994884-T-G, CADD 5.18
- P25T (p.Pro25Thr), Ensembl rs376726233, REVEL 0.05, CADD 15.70, Uncertain significance, not specified
- P25A (p.Pro25Ala), gnomAD 15-73994885-C-G, REVEL 0.04, CADD 14.60
- P25S (p.Pro25Ser), gnomAD 15-73994885-C-T, REVEL 0.03, CADD 11.90
- P25H (p.Pro25His), gnomAD 15-73994886-C-A, REVEL 0.08, CADD 22.60
- P25P (p.Pro25Pro), rs1277864933, gnomAD 15-73994887-C-A, CADD 8.40
- P26A (p.Pro26Ala), gnomAD rs1346221283, REVEL 0.07, CADD 19.80
- P26H (p.Pro26His), ExAC rs781165510, TOPMed rs781165510, gnomAD rs781165510, REVEL 0.06, CADD 22.60
- P26R (p.Pro26Arg), ExAC rs781165510, TOPMed rs781165510, gnomAD rs781165510, REVEL 0.07, CADD 17.70
- P26T (p.Pro26Thr), gnomAD rs1346221283, REVEL 0.10, CADD 22.90
- P26S (p.Pro26Ser), gnomAD 15-73994888-C-T, REVEL 0.08, CADD 23.00
- P26L (p.Pro26Leu), gnomAD 15-73994889-C-T, REVEL 0.07, CADD 22.60
- P26P (p.Pro26Pro), gnomAD 15-73994890-C-A, CADD 4.56
- E27D (p.Glu27Asp), TOPMed rs979739048, gnomAD rs979739048, REVEL 0.04, CADD 5.94
- E27R (p.Glu27Arg), gnomAD 15-73994884-TC-T, CADD 21.30
- E27Q (p.Glu27Gln), gnomAD 15-73994891-G-C, REVEL 0.07, CADD 20.90
- E27* (p.Glu27Ter), gnomAD 15-73994891-G-T, CADD 34.00
- E27G (p.Glu27Gly), gnomAD 15-73994892-A-G, REVEL 0.02, CADD 20.20
- T28I (p.Thr28Ile), ExAC rs201524800, TOPMed rs201524800, gnomAD rs201524800, REVEL 0.01, CADD 11.20
- T28P (p.Thr28Pro), rs28504405, ClinGen CA7652301, ClinVar RCV000957320, 1000Genomes rs28504405, REVEL 0.04, CADD 0.29, Benign, not provided
- T28S (p.Thr28Ser), gnomAD 15-73994894-A-T, REVEL 0.04, CADD 0.01
- T28N (p.Thr28Asn), gnomAD 15-73994895-C-A, REVEL 0.01, CADD 3.41
- T28T (p.Thr28Thr), gnomAD 15-73994896-C-T, CADD 5.39
- P29A (p.Pro29Ala), ExAC rs749399804, gnomAD rs749399804, REVEL 0.01, CADD 2.70
- P29L (p.Pro29Leu), Ensembl rs959506424, REVEL 0.03, CADD 6.31
- P29S (p.Pro29Ser), ExAC rs749399804, gnomAD rs749399804, REVEL 0.02, CADD 7.70
- P29T (p.Pro29Thr), ExAC rs749399804, gnomAD rs749399804, REVEL 0.02, CADD 8.71
- P29H (p.Pro29His), gnomAD 15-73994898-C-A, REVEL 0.04, CADD 12.80
- P29P (p.Pro29Pro), gnomAD 15-73994899-C-A, CADD 8.34
- S30P (p.Ser30Pro), Ensembl rs1369762288, REVEL 0.01, CADD 9.12
- S30T (p.Ser30Thr), Ensembl rs1369762288, REVEL 0.00, CADD 5.43
- S30Y (p.Ser30Tyr), gnomAD 15-73994901-C-A, REVEL 0.10, CADD 17.80
- S30S (p.Ser30Ser), gnomAD 15-73994902-T-C, CADD 4.01
- E31K (p.Glu31Lys), ExAC rs768816135, TOPMed rs768816135, gnomAD rs768816135, REVEL 0.17, CADD 25.50, Uncertain significance, not specified
- E31* (p.Glu31Ter), gnomAD 15-73994903-G-T, CADD 36.00
- E31D (p.Glu31Asp), gnomAD 15-73994905-A-T, REVEL 0.08, CADD 19.70
- G32D (p.Gly32Asp), gnomAD rs1191059573, REVEL 0.03, CADD 0.60
- G32C (p.Gly32Cys), gnomAD 15-73994906-G-T, REVEL 0.05, CADD 23.00
- G32G (p.Gly32Gly), gnomAD 15-73994908-C-A, CADD 6.81
- R33C (p.Arg33Cys), gnomAD rs1480567758
- R33H (p.Arg33His), Ensembl rs2069395846, REVEL 0.02, CADD 4.82
- R33S (p.Arg33Ser), gnomAD 15-73994909-C-A, REVEL 0.04, CADD 17.10
- R33L (p.Arg33Leu), gnomAD 15-73994910-G-T, REVEL 0.01, CADD 15.00
- R33R (p.Arg33Arg), gnomAD 15-73994911-C-A, CADD 2.90
- Q34P (p.Gln34Pro), gnomAD rs1200903609
- Q34R (p.Gln34Arg), gnomAD rs1200903609, REVEL 0.05, CADD 6.43
- Q34K (p.Gln34Lys), gnomAD 15-73994912-C-A, REVEL 0.02, CADD 12.30
- p.Gln34 Pro35insAlaSer, gnomAD 15-73994914-G-GGC, CADD 10.90
- Q34Q (p.Gln34Gln), gnomAD 15-73994914-G-A, CADD 6.05
- Q34H (p.Gln34His), gnomAD 15-73994914-G-T, REVEL 0.04, CADD 16.40
- P35H (p.Pro35His), TOPMed rs2069396424, REVEL 0.07, CADD 19.80
- P35S (p.Pro35Ser), gnomAD 15-73994915-C-T, REVEL 0.02, CADD 3.28
Public PML analysis runs
- PML analysis run — PML (1,384 variants) — completed 2026-08-21