PDCD1 (Programmed cell death protein 1) variants and mutations
PDCD1 (also known as Programmed cell death protein 1) is a human protein-coding gene encoding a programmed cell death protein 1 protein. PDCD1 is an inhibitory receptor on activated T cells that binds PD-L1 and PD-L2. Its signaling helps maintain immune tolerance by restraining T-cell activation, making the protein important in autoimmunity and cancer immunotherapy. This analysis covers 903 PDCD1 variants and mutations. Of these, 74% have computational variant effect predictions. Disease context includes melanoma, non-small cell lung carcinoma, and renal cell carcinoma. Example PDCD1 variants include Q2*, Q5H, and Q5P.
Variant analysis overview
- Gene: PDCD1
- Protein: Programmed cell death protein 1
- UniProt accession: Q15116
- Organism: Homo sapiens
- Variants analyzed: 903
- Variant scope: all variants
- Completed: 2026-07-26
Variant and mutation evidence
- Variant composition: 738 unspecified-consequence records; 50 missense variants; 7 frameshift variants; 1 in-frame insertions; 92 synonymous variants; 3 stop-gained variants; 2 in-frame deletions; 4 splice-region variants; 6 substitution
- Prediction scores: 668 variants have prediction scores (74% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: melanoma, non-small cell lung carcinoma, renal cell carcinoma, esophageal squamous cell carcinoma, neoplasm, nasopharyngeal carcinoma, head and neck squamous cell carcinoma, Hodgkins lymphoma, endometrial cancer, squamous cell carcinoma, metastatic melanoma, gastric cancer.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 7 post-translational modification sites.
- Structural context: 374 variants have structural context.
- PTM context: 27 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 PDCD1 variants
Examples include Q2*, Q5H, Q5P, Q5R, A6P, A6V, P9S, V11A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- Q2* (p.Gln2Ter), Ensembl rs866088771, CADD 33.00
- Q5H (p.Gln5His), TOPMed rs1448793282, gnomAD rs1448793282, REVEL 0.07, MetaLR 0.15
- Q5P (p.Gln5Pro), gnomAD rs1189066887, REVEL 0.06, MetaLR 0.11
- Q5R (p.Gln5Arg), gnomAD rs1189066887, REVEL 0.04, MetaLR 0.08
- A6P (p.Ala6Pro), Ensembl rs1033748408, REVEL 0.13, MetaLR 0.17
- A6V (p.Ala6Val), ExAC rs769034572, TOPMed rs769034572, gnomAD rs769034572, REVEL 0.02, MetaLR 0.07
- P9S (p.Pro9Ser), Ensembl rs2124872244, REVEL 0.02, MetaLR 0.10
- V11A (p.Val11Ala), gnomAD rs1357299712, REVEL 0.07, MetaLR 0.13
- V11I (p.Val11Ile), rs142544044, ClinGen CA2223466, ClinVar RCV004210277, ESP rs142544044, REVEL 0.05, MetaLR 0.11, Uncertain significance, not specified
- A13V (p.Ala13Val), rs777215737, ClinGen CA2223465, ClinVar RCV004099908, ExAC rs777215737, REVEL 0.10, MetaLR 0.14, Uncertain significance, not specified
- L15I (p.Leu15Ile), gnomAD rs1268978816, REVEL 0.17, MetaLR 0.32
- Q16* (p.Gln16Ter), gnomAD rs1350859521, CADD 36.00
- L17P (p.Leu17Pro), Ensembl rs2124872179
- W19* (p.Trp19Ter), Ensembl rs2124872162, CADD 35.00
- R20Q (p.Arg20Gln), ESP rs368550965, ExAC rs368550965, TOPMed rs368550965, gnomAD rs368550965, REVEL 0.06, MetaLR 0.11
- R20W (p.Arg20Trp), rs866653159, TOPMed rs866653159, gnomAD rs866653159, NCI-TCGA Cosmic COSV5769, REVEL 0.07, MetaLR 0.10, Variant assessed as somatic; moderate impact.
- P21A (p.Pro21Ala), ExAC rs754849604, gnomAD rs754849604
- P21Q (p.Pro21Gln), TOPMed rs1388107514, gnomAD rs1388107514, REVEL 0.19, MetaLR 0.14
- P21S (p.Pro21Ser), ExAC rs754849604, gnomAD rs754849604, REVEL 0.03, MetaLR 0.10
- W23* (p.Trp23Ter), ExAC rs753651738, TOPMed rs753651738, gnomAD rs753651738, CADD 36.00
- W23L (p.Trp23Leu), ExAC rs753651738, TOPMed rs753651738, gnomAD rs753651738, REVEL 0.22, MetaLR 0.13
- W23S (p.Trp23Ser), ExAC rs753651738, TOPMed rs753651738, gnomAD rs753651738, REVEL 0.21, MetaLR 0.12
- F24L (p.Phe24Leu), Ensembl rs2124872119, REVEL 0.04, MetaLR 0.04
- L25V (p.Leu25Val), gnomAD rs1192883440, REVEL 0.12, MetaLR 0.23
- D26A (p.Asp26Ala), Ensembl rs2124861799
- D26E (p.Asp26Glu), Ensembl rs2124861792, REVEL 0.03, MetaLR 0.07
- D26G (p.Asp26Gly), Ensembl rs2124861799
- D26V (p.Asp26Val), Ensembl rs2124861799
- S27C (p.Ser27Cys), ExAC rs756045758, gnomAD rs756045758
- S27F (p.Ser27Phe), ExAC rs756045758, gnomAD rs756045758, REVEL 0.09, MetaLR 0.13
- S27P (p.Ser27Pro), Ensembl rs2124861785, REVEL 0.04, MetaLR 0.12
- S27T (p.Ser27Thr), Ensembl rs2124861785
- S27Y (p.Ser27Tyr), ExAC rs756045758, gnomAD rs756045758, REVEL 0.16, MetaLR 0.14
- S27R (p.Ser27Arg), rs866487309, []
- P28L (p.Pro28Leu), 1000Genomes rs56234260, ESP rs56234260, ExAC rs56234260, TOPMed rs56234260, REVEL 0.03, MetaLR 0.11
- P28S (p.Pro28Ser), ExAC rs750373757, gnomAD rs750373757, REVEL 0.02, MetaLR 0.11
- D29A (p.Asp29Ala), Ensembl rs1017421889
- D29E (p.Asp29Glu), Ensembl rs2124861739, REVEL 0.07, MetaLR 0.11
- D29G (p.Asp29Gly), Ensembl rs1017421889
- D29H (p.Asp29His), TOPMed rs1700939528, gnomAD rs1700939528
- D29N (p.Asp29Asn), TOPMed rs1700939528, gnomAD rs1700939528, MetaLR 0.11, MetaSVM -1.07
- D29V (p.Asp29Val), Ensembl rs1017421889, REVEL 0.04, MetaLR 0.15
- D29Y (p.Asp29Tyr), TOPMed rs1700939528, gnomAD rs1700939528, REVEL 0.06, MetaLR 0.11
- R30G (p.Arg30Gly), Ensembl rs2124861731, REVEL 0.10, MetaLR 0.13
- R30K (p.Arg30Lys), gnomAD rs1412459900, REVEL 0.01, MetaLR 0.11
- R30M (p.Arg30Met), gnomAD rs1412459900, REVEL 0.17, MetaLR 0.20
- R30S (p.Arg30Ser), Ensembl rs866487309, REVEL 0.11, MetaLR 0.14
- R30T (p.Arg30Thr), gnomAD rs1412459900, MetaLR 0.14, MetaSVM -0.97
- P31L (p.Pro31Leu), ExAC rs751727384, TOPMed rs751727384, gnomAD rs751727384, MetaLR 0.13, MetaSVM -0.97
- P31S (p.Pro31Ser), ExAC rs757336262, TOPMed rs757336262, gnomAD rs757336262, REVEL 0.05, MetaLR 0.13
- P31T (p.Pro31Thr), ExAC rs757336262, TOPMed rs757336262, gnomAD rs757336262, REVEL 0.17, MetaLR 0.15
- W32C (p.Trp32Cys), NCI-TCGA TCGA novel, Ensembl rs2124861673, REVEL 0.07, MetaLR 0.14, Variant assessed as somatic; moderate impact.
- W32L (p.Trp32Leu), Ensembl rs2124861685, REVEL 0.17, MetaLR 0.14
- W32R (p.Trp32Arg), Ensembl rs2124861691, REVEL 0.06, MetaLR 0.13
- W32S (p.Trp32Ser), Ensembl rs2124861685, MetaLR 0.13, MetaSVM -1.01
- N33I (p.Asn33Ile), Ensembl rs2124861662
- N33K (p.Asn33Lys), 1000Genomes rs533755778, gnomAD rs533755778, REVEL 0.06, MetaLR 0.08
- N33S (p.Asn33Ser), Ensembl rs2124861662, MetaLR 0.04, MetaSVM -0.97
- N33T (p.Asn33Thr), Ensembl rs2124861662, REVEL 0.03, MetaLR 0.10
- P34A (p.Pro34Ala), ExAC rs763228671, TOPMed rs763228671, gnomAD rs763228671, REVEL 0.03, MetaLR 0.12
- P34L (p.Pro34Leu), Ensembl rs2124861642, MetaLR 0.12, MetaSVM -0.98
- P34S (p.Pro34Ser), ExAC rs763228671, TOPMed rs763228671, gnomAD rs763228671, REVEL 0.03, MetaLR 0.11
- P34T (p.Pro34Thr), ExAC rs763228671, TOPMed rs763228671, gnomAD rs763228671, REVEL 0.07, MetaLR 0.17
- P35H (p.Pro35His), TOPMed rs1700938702, REVEL 0.17, MetaLR 0.11
- P35L (p.Pro35Leu), TOPMed rs1700938702, REVEL 0.10, MetaLR 0.02
- P35R (p.Pro35Arg), TOPMed rs1700938702
- P35S (p.Pro35Ser), Ensembl rs2124861633, MetaLR 0.09, MetaSVM -1.02
- T36A (p.Thr36Ala), 1000Genomes rs373081859, ESP rs373081859, ExAC rs373081859, TOPMed rs373081859, REVEL 0.25, MetaLR 0.26
- T36I (p.Thr36Ile), Ensembl rs2124861594
- T36P (p.Thr36Pro), 1000Genomes rs373081859, ESP rs373081859, ExAC rs373081859, TOPMed rs373081859
- T36S (p.Thr36Ser), Ensembl rs2124861594, MetaLR 0.20, MetaSVM -0.89
- F37I (p.Phe37Ile), Ensembl rs2124861581
- F37L (p.Phe37Leu), Ensembl rs2124861581
- F37S (p.Phe37Ser), Ensembl rs2124861571, MetaLR 0.05, MetaSVM -1.08
- S38F (p.Ser38Phe), rs1243031095, gnomAD rs1243031095, NCI-TCGA Cosmic COSV5769, AlphaMissense 0.13, MetaLR 0.21, Variant assessed as somatic; moderate impact.
- S38P (p.Ser38Pro), Ensembl rs2124861562
- S38T (p.Ser38Thr), Ensembl rs2124861562
- P39A (p.Pro39Ala), Ensembl rs2124861544
- P39L (p.Pro39Leu), Ensembl rs2124861539, REVEL 0.22, MetaLR 0.47
- P39Q (p.Pro39Gln), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P39S (p.Pro39Ser), Ensembl rs2124861544, MetaLR 0.50, MetaSVM -0.46
- A40G (p.Ala40Gly), Ensembl rs2124861522
- A40P (p.Ala40Pro), Ensembl rs2124861525
- A40S (p.Ala40Ser), Ensembl rs2124861525, REVEL 0.04, MetaLR 0.15
- A40T (p.Ala40Thr), Ensembl rs2124861525, REVEL 0.03, MetaLR 0.14
- A40V (p.Ala40Val), Ensembl rs2124861522, REVEL 0.20, MetaLR 0.20
- L41P (p.Leu41Pro), Ensembl rs2124861506, REVEL 0.04, MetaLR 0.12
- L41Q (p.Leu41Gln), Ensembl rs2124861506, MetaLR 0.07, MetaSVM -1.02
- L42F (p.Leu42Phe), Ensembl rs2124861493, REVEL 0.18, MetaLR 0.47
- L42H (p.Leu42His), Ensembl rs2124861485
- V43A (p.Val43Ala), Ensembl rs2124861459
- V43E (p.Val43Glu), Ensembl rs2124861459
- V43G (p.Val43Gly), Ensembl rs2124861459, MetaLR 0.20, MetaSVM -0.93
- V43L (p.Val43Leu), ESP rs368829632, ExAC rs368829632, TOPMed rs368829632, gnomAD rs368829632, REVEL 0.07, MetaLR 0.13
- V43M (p.Val43Met), rs368829632, ESP rs368829632, ExAC rs368829632, TOPMed rs368829632, REVEL 0.06, MetaLR 0.13, Variant assessed as somatic; moderate impact.
- V44L (p.Val44Leu), Ensembl rs2124861447, REVEL 0.34, MetaLR 0.38
- V44M (p.Val44Met), Ensembl rs2124861447
- T45A (p.Thr45Ala), Ensembl rs2124861435, REVEL 0.07, MetaLR 0.10
- T45I (p.Thr45Ile), Ensembl rs2124861428
- T45S (p.Thr45Ser), Ensembl rs2124861435, MetaLR 0.06, MetaSVM -1.00
- E46* (p.Glu46Ter), TOPMed rs1429395114, gnomAD rs1429395114, CADD 36.00
- E46D (p.Glu46Asp), Ensembl rs1700937587
- E46G (p.Glu46Gly), Ensembl rs2124861400
- E46K (p.Glu46Lys), TOPMed rs1429395114, gnomAD rs1429395114, REVEL 0.47, MetaLR 0.46
- E46Q (p.Glu46Gln), TOPMed rs1429395114, gnomAD rs1429395114, MetaLR 0.39, MetaSVM -0.65
- G47A (p.Gly47Ala), Ensembl rs2124861379
- G47E (p.Gly47Glu), Ensembl rs2124861379
- G47R (p.Gly47Arg), Ensembl rs1700937498
- G47V (p.Gly47Val), Ensembl rs2124861379, MetaLR 0.70, MetaSVM 0.51
- G47W (p.Gly47Trp), Ensembl rs1700937498, REVEL 0.60, MetaLR 0.70
- D48A (p.Asp48Ala), Ensembl rs2124861350
- D48E (p.Asp48Glu), gnomAD rs1314754290
- D48G (p.Asp48Gly), Ensembl rs2124861350
- D48H (p.Asp48His), Ensembl rs1218751742
- D48N (p.Asp48Asn), Ensembl rs1218751742
- D48V (p.Asp48Val), Ensembl rs2124861350, MetaLR 0.04, MetaSVM -1.01
- D48Y (p.Asp48Tyr), Ensembl rs1218751742, REVEL 0.05, MetaLR 0.05
- N49H (p.Asn49His), Ensembl rs2124861330
- N49I (p.Asn49Ile), Ensembl rs2124861321
- N49K (p.Asn49Lys), 1000Genomes rs141718335, ESP rs141718335, ExAC rs141718335, TOPMed rs141718335
- N49S (p.Asn49Ser), Ensembl rs2124861321, REVEL 0.03, MetaLR 0.14
- N49T (p.Asn49Thr), Ensembl rs2124861321
- N49Y (p.Asn49Tyr), Ensembl rs2124861330
- A50D (p.Ala50Asp), Ensembl rs2124861291, REVEL 0.52, MetaLR 0.44
- A50G (p.Ala50Gly), Ensembl rs2124861291
- A50P (p.Ala50Pro), TOPMed rs1203794937, gnomAD rs1203794937
- A50T (p.Ala50Thr), TOPMed rs1203794937, gnomAD rs1203794937, REVEL 0.36, MetaLR 0.39
- A50V (p.Ala50Val), Ensembl rs2124861291, REVEL 0.09, MetaLR 0.09
- T51I (p.Thr51Ile), TOPMed rs1485804549, gnomAD rs1485804549, REVEL 0.33, MetaLR 0.48
- T51S (p.Thr51Ser), TOPMed rs1485804549, gnomAD rs1485804549, MetaLR 0.36, MetaSVM -0.64
- F52I (p.Phe52Ile), Ensembl rs2124861256
- F52L (p.Phe52Leu), Ensembl rs2124861256, MetaLR 0.37, MetaSVM -0.23
- T53I (p.Thr53Ile), Ensembl rs1700936959
- T53P (p.Thr53Pro), Ensembl rs2124861250
- T53S (p.Thr53Ser), Ensembl rs2124861250, MetaLR 0.15, MetaSVM -0.98
- C54* (p.Cys54Ter), TOPMed rs1291136724, gnomAD rs1291136724, CADD 36.00
- C54R (p.Cys54Arg), Ensembl rs2124861238
- C54S (p.Cys54Ser), Ensembl rs2124861238, REVEL 0.55, MetaLR 0.43
- C54W (p.Cys54Trp), TOPMed rs1291136724, gnomAD rs1291136724, MetaLR 0.42, MetaSVM -0.12
- S55C (p.Ser55Cys), Ensembl rs2124861211
- S55G (p.Ser55Gly), Ensembl rs2124861211
- S55N (p.Ser55Asn), Ensembl rs2124861204
- S55R (p.Ser55Arg), 1000Genomes rs55993679, ExAC rs55993679, TOPMed rs55993679, gnomAD rs55993679, REVEL 0.27, MetaLR 0.29
- S55T (p.Ser55Thr), Ensembl rs2124861204, MetaLR 0.23, MetaSVM -0.83
- F56I (p.Phe56Ile), Ensembl rs2124861190
- F56L (p.Phe56Leu), Ensembl rs2124861190
- F56S (p.Phe56Ser), Ensembl rs2124861185, MetaLR 0.37, MetaSVM -0.68
- S57F (p.Ser57Phe), Ensembl rs2124861162
- S57P (p.Ser57Pro), Ensembl rs2124861171
- S57T (p.Ser57Thr), Ensembl rs2124861171
- N58D (p.Asn58Asp), TOPMed rs1222512746, gnomAD rs1222512746, REVEL 0.02, MetaLR 0.05
- N58I (p.Asn58Ile), Ensembl rs2124861138, MetaLR 0.10, MetaSVM -0.99
- T59I (p.Thr59Ile), Ensembl rs2124861126
- T59R (p.Thr59Arg), Ensembl rs2124861126
- T59S (p.Thr59Ser), Ensembl rs2124861134, MetaLR 0.16, MetaSVM -0.93
- S60* (p.Ser60Ter), ExAC rs779874434, TOPMed rs779874434, gnomAD rs779874434, CADD 35.00
- S60L (p.Ser60Leu), rs779874434, NCI-TCGA Cosmic COSV5769, ExAC rs779874434, TOPMed rs779874434, REVEL 0.07, MetaLR 0.04, Variant assessed as somatic; moderate impact.
- S60P (p.Ser60Pro), Ensembl rs2124861114
- S60T (p.Ser60Thr), Ensembl rs2124861114
- S60W (p.Ser60Trp), ExAC rs779874434, TOPMed rs779874434, gnomAD rs779874434, REVEL 0.10, MetaLR 0.14
- E61* (p.Glu61Ter), Ensembl rs2124861092
- E61D (p.Glu61Asp), TOPMed rs1000249974, gnomAD rs1000249974, REVEL 0.04, MetaLR 0.09
- E61G (p.Glu61Gly), Ensembl rs2124861086
- E61K (p.Glu61Lys), Ensembl rs2124861092
- E61Q (p.Glu61Gln), Ensembl rs2124861092
- E61V (p.Glu61Val), Ensembl rs2124861086, MetaLR 0.14, MetaSVM -0.95
- S62C (p.Ser62Cys), Ensembl rs2124861069
- S62N (p.Ser62Asn), Ensembl rs1473786321, REVEL 0.01, MetaLR 0.04
- F63I (p.Phe63Ile), Ensembl rs2124861058
- F63L (p.Phe63Leu), ExAC rs781123013, TOPMed rs781123013, gnomAD rs781123013, REVEL 0.03, MetaLR 0.05
- F63Y (p.Phe63Tyr), Ensembl rs2124861054, MetaLR 0.07, MetaSVM -1.08
- V64E (p.Val64Glu), ESP rs142434414, TOPMed rs142434414, gnomAD rs142434414
- V64G (p.Val64Gly), ESP rs142434414, TOPMed rs142434414, gnomAD rs142434414, REVEL 0.22, MetaLR 0.33
- V64L (p.Val64Leu), gnomAD rs1319637878
- V64M (p.Val64Met), gnomAD rs1319637878, REVEL 0.08, MetaLR 0.13
- L65P (p.Leu65Pro), Ensembl rs2124861011
- L65Q (p.Leu65Gln), Ensembl rs2124861011
- L65V (p.Leu65Val), ExAC rs757247111, TOPMed rs757247111, gnomAD rs757247111
- N66T (p.Asn66Thr), Ensembl rs28615468, MetaLR 0.39, MetaSVM -0.05
- W67* (p.Trp67Ter), Ensembl rs2124860980, CADD 37.00
Public PDCD1 analysis runs
- PDCD1 analysis run — PDCD1 (903 variants) — completed 2026-07-26