CD274 (Programmed cell death 1 ligand 1) variants and mutations
CD274 (also known as Programmed cell death 1 ligand 1) is a human protein-coding gene encoding a programmed cell death 1 ligand 1 protein. By engaging PD-1, it suppresses activated T cells by engaging PD-1 and thereby limits immune-mediated tissue damage. Many cancers exploit high PD-L1 expression to evade immune attack, making the PD-1/PD-L1 axis a central target of immune-checkpoint therapy. This analysis covers 1,340 CD274 variants and mutations. Of these, 55% have computational variant effect predictions. Disease context includes non-small cell lung carcinoma, Merkel cell skin cancer, and small cell lung carcinoma. Example CD274 variants include R2S, R2T, and R2W.
Variant analysis overview
- Gene: CD274
- Protein: Programmed cell death 1 ligand 1
- UniProt accession: Q9NZQ7
- Organism: Homo sapiens
- Variants analyzed: 1340
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,159 unspecified-consequence records; 49 missense variants; 115 synonymous variants; 4 splice-region variants; 5 frameshift variants; 2 in-frame insertions; 2 stop-gained variants; 2 in-frame deletions; 2 substitution
- Prediction scores: 740 variants have prediction scores (55% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: non-small cell lung carcinoma, Merkel cell skin cancer, small cell lung carcinoma, hepatocellular carcinoma, head and neck squamous cell carcinoma, neoplasm, urothelial carcinoma, breast cancer, lung cancer, esophageal squamous cell carcinoma, urinary bladder carcinoma, gastric adenocarcinoma.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 2 domains; 4 post-translational modification sites.
- Structural context: 1,094 variants have structural context.
- PTM context: 18 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 CD274 variants
Examples include R2S, R2T, R2W, R2K, I3M, I3V, F4C, F4S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- R2S (p.Arg2Ser), Ensembl rs2131208624, REVEL 0.10, AlphaMissense 0.42
- R2T (p.Arg2Thr), Ensembl rs1819297505
- R2W (p.Arg2Trp), Ensembl rs2131208613
- R2K (p.Arg2Lys), gnomAD 9-5456118-G-A, REVEL 0.02, AlphaMissense 0.16
- I3M (p.Ile3Met), gnomAD rs1433541247, REVEL 0.03, AlphaMissense 0.15
- I3V (p.Ile3Val), gnomAD 9-5456120-A-G, REVEL 0.08, AlphaMissense 0.12
- F4C (p.Phe4Cys), ExAC rs748476315, TOPMed rs748476315, gnomAD rs748476315, REVEL 0.02, AlphaMissense 0.22
- F4S (p.Phe4Ser), ExAC rs748476315, TOPMed rs748476315, gnomAD rs748476315, MetaLR 0.08, MetaSVM -0.99
- F4Y (p.Phe4Tyr), ExAC rs748476315, TOPMed rs748476315, gnomAD rs748476315, REVEL 0.02, AlphaMissense 0.19
- A5D (p.Ala5Asp), NCI-TCGA Cosmic COSV6750, cosmic curated COSV67502, REVEL 0.09, AlphaMissense 0.37, Variant assessed as somatic; moderate impact.
- A5G (p.Ala5Gly), Ensembl rs2131208656, MetaLR 0.08, MetaSVM -0.93
- A5P (p.Ala5Pro), cosmic curated COSV10105, 1000Genomes rs139709512, ESP rs139709512, ExAC rs139709512, REVEL 0.03, AlphaMissense 0.15
- A5S (p.Ala5Ser), 1000Genomes rs139709512, ESP rs139709512, ExAC rs139709512, TOPMed rs139709512, REVEL 0.01, AlphaMissense 0.11
- A5V (p.Ala5Val), Ensembl rs2131208656, REVEL 0.03, AlphaMissense 0.15
- A5T (p.Ala5Thr), gnomAD 9-5456126-G-A, REVEL 0.02, AlphaMissense 0.12
- A5A (p.Ala5Ala), rs577786663, gnomAD 9-5456128-T-C, CADD 2.60
- V6D (p.Val6Asp), Ensembl rs1819298033
- V6F (p.Val6Phe), TOPMed rs1586762927, gnomAD rs1586762927, REVEL 0.12, AlphaMissense 0.09
- V6G (p.Val6Gly), Ensembl rs1819298033
- V6I (p.Val6Ile), TOPMed rs1586762927, gnomAD rs1586762927
- V6L (p.Val6Leu), TOPMed rs1586762927, gnomAD rs1586762927, REVEL 0.06, AlphaMissense 0.14
- V6V (p.Val6Val), gnomAD 9-5456131-C-A, CADD 0.69
- F7C (p.Phe7Cys), gnomAD rs1401088731, REVEL 0.18, AlphaMissense 0.15
- F7I (p.Phe7Ile), Ensembl rs2131208696, MetaLR 0.05, MetaSVM -0.98
- I8L (p.Ile8Leu), TOPMed rs981554963, MetaLR 0.07, MetaSVM -0.99
- I8V (p.Ile8Val), TOPMed rs981554963, REVEL 0.02, AlphaMissense 0.09
- I8T (p.Ile8Thr), gnomAD 9-5456136-T-C, REVEL 0.02, AlphaMissense 0.09
- I8K (p.Ile8Lys), gnomAD 9-5456136-T-A, REVEL 0.15, AlphaMissense 0.37
- I8M (p.Ile8Met), gnomAD 9-5456137-A-G, REVEL 0.03, AlphaMissense 0.14
- F9L (p.Phe9Leu), Ensembl rs2131208723, REVEL 0.03, AlphaMissense 0.49
- F9F (p.Phe9Phe), rs2131208723, gnomAD 9-5456140-C-T, CADD 6.14
- M10I (p.Met10Ile), Ensembl rs2131208750
- M10K (p.Met10Lys), Ensembl rs2131208741, MetaLR 0.08, MetaSVM -0.98
- M10L (p.Met10Leu), gnomAD rs1461605894, REVEL 0.10, AlphaMissense 0.12
- M10T (p.Met10Thr), Ensembl rs2131208741, REVEL 0.02, AlphaMissense 0.11
- T11S (p.Thr11Ser), Ensembl rs2131208765, MetaLR 0.06, MetaSVM -1.00
- T11T (p.Thr11Thr), rs760293478, gnomAD 9-5456146-C-T, CADD 7.13
- Y12* (p.Tyr12Ter), Ensembl rs2131208793, NCI-TCGA TCGA novel, CADD 38.00, Variant assessed as somatic; high impact.
- Y12C (p.Tyr12Cys), cosmic curated COSV67501, Ensembl rs2131208789
- Y12F (p.Tyr12Phe), Ensembl rs2131208789
- Y12H (p.Tyr12His), Ensembl rs2131208782
- Y12N (p.Tyr12Asn), Ensembl rs2131208782, MetaLR 0.10, MetaSVM -0.97
- W13* (p.Trp13Ter), cosmic curated COSV10593, ExAC rs776345482, TOPMed rs776345482, gnomAD rs776345482
- W13C (p.Trp13Cys), ExAC rs776345482, TOPMed rs776345482, gnomAD rs776345482, REVEL 0.10, AlphaMissense 0.10
- W13R (p.Trp13Arg), ExAC rs765955659, gnomAD rs765955659, REVEL 0.09, AlphaMissense 0.20
- W13S (p.Trp13Ser), Ensembl rs2131208805, MetaLR 0.09, MetaSVM -1.04
- W13G (p.Trp13Gly), gnomAD 9-5456150-T-G, REVEL 0.07, AlphaMissense 0.07
- H14D (p.His14Asp), gnomAD rs1819298566, MetaLR 0.06, MetaSVM -0.99
- H14L (p.His14Leu), Ensembl rs2131208821, REVEL 0.12, AlphaMissense 0.12
- H14Y (p.His14Tyr), gnomAD rs1819298566, REVEL 0.09, AlphaMissense 0.08
- H14N (p.His14Asn), gnomAD 9-5456153-C-A, REVEL 0.08, AlphaMissense 0.13
- H14R (p.His14Arg), gnomAD 9-5456154-A-G, REVEL 0.12, AlphaMissense 0.11
- L15F (p.Leu15Phe), Ensembl rs2131208833
- L15M (p.Leu15Met), Ensembl rs2131208824, MetaLR 0.23, MetaSVM -0.89
- L16M (p.Leu16Met), Ensembl rs2131208847, REVEL 0.13, AlphaMissense 0.18
- L16V (p.Leu16Val), Ensembl rs2131208847, MetaLR 0.06, MetaSVM -1.00
- L16L (p.Leu16Leu), rs2131208857, gnomAD 9-5456161-G-A, CADD 7.87
- N17D (p.Asn17Asp), Ensembl rs1819298628
- N17H (p.Asn17His), Ensembl rs1819298628, REVEL 0.07, AlphaMissense 0.06
- N17I (p.Asn17Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N17K (p.Asn17Lys), ExAC rs750730511, gnomAD rs750730511, REVEL 0.05, AlphaMissense 0.09
- N17S (p.Asn17Ser), Ensembl rs2131208869
- N17Y (p.Asn17Tyr), Ensembl rs1819298628, MetaLR 0.10, MetaSVM -1.02
- N17N (p.Asn17Asn), rs750730511, gnomAD 9-5456164-C-T, CADD 0.06
- A18E (p.Ala18Glu), Ensembl rs2131210878, REVEL 0.20, AlphaMissense 0.64
- A18G (p.Ala18Gly), Ensembl rs2131210878
- A18P (p.Ala18Pro), TOPMed rs1243212672, gnomAD rs1243212672, REVEL 0.21, AlphaMissense 0.39
- A18T (p.Ala18Thr), rs1243212672, NCI-TCGA Cosmic COSV6750, cosmic curated COSV67501, TOPMed rs1243212672, REVEL 0.15, AlphaMissense 0.36, Variant assessed as somatic; moderate impact.
- A18V (p.Ala18Val), Ensembl rs2131210878
- A18S (p.Ala18Ser), gnomAD 9-5456165-G-T, REVEL 0.16, AlphaMissense 0.21
- A18A (p.Ala18Ala), rs200003059, gnomAD 9-5457080-A-G, CADD 9.01
- F19L (p.Phe19Leu), TOPMed rs1405569371, gnomAD rs1405569371
- F19S (p.Phe19Ser), Ensembl rs2131210891, SIFT 0.00
- F19F (p.Phe19Phe), rs1405569371, gnomAD 9-5457083-T-C, CADD 11.60
- T20A (p.Thr20Ala), Ensembl rs1563802741
- T20I (p.Thr20Ile), TOPMed rs937227717, SIFT 0.01
- T20S (p.Thr20Ser), TOPMed rs937227717, REVEL 0.12, AlphaMissense 0.20
- T20T (p.Thr20Thr), rs762851891, gnomAD 9-5457086-T-C, CADD 4.77
- V21F (p.Val21Phe), ESP rs370800260, ExAC rs370800260, TOPMed rs370800260, gnomAD rs370800260
- V21I (p.Val21Ile), ESP rs370800260, ExAC rs370800260, TOPMed rs370800260, gnomAD rs370800260, REVEL 0.08, AlphaMissense 0.08, Likely benign, not specified
- V21L (p.Val21Leu), ESP rs370800260, ExAC rs370800260, TOPMed rs370800260, gnomAD rs370800260, SIFT 0.01
- V21V (p.Val21Val), rs1204651428, gnomAD 9-5457089-C-G, CADD 8.78
- T22K (p.Thr22Lys), ESP rs143235887, ExAC rs143235887, TOPMed rs143235887, gnomAD rs143235887
- T22M (p.Thr22Met), ESP rs143235887, ExAC rs143235887, TOPMed rs143235887, gnomAD rs143235887, REVEL 0.29, AlphaMissense 0.10
- T22P (p.Thr22Pro), Ensembl rs2131210935
- T22R (p.Thr22Arg), ESP rs143235887, ExAC rs143235887, TOPMed rs143235887, gnomAD rs143235887
- T22S (p.Thr22Ser), Ensembl rs2131210935, SIFT 0.02
- T22T (p.Thr22Thr), rs146564807, gnomAD 9-5457092-G-A, CADD 5.25
- V23D (p.Val23Asp), Ensembl rs2131210963
- V23F (p.Val23Phe), gnomAD rs1485681345, SIFT 0.00
- V23I (p.Val23Ile), gnomAD rs1485681345, REVEL 0.13, AlphaMissense 0.12
- V23L (p.Val23Leu), gnomAD rs1485681345, REVEL 0.32, AlphaMissense 0.46
- P24A (p.Pro24Ala), ExAC rs766519356, gnomAD rs766519356, SIFT 0.04
- P24L (p.Pro24Leu), gnomAD rs1416019385, REVEL 0.23, AlphaMissense 0.20
- P24S (p.Pro24Ser), rs766519356, NCI-TCGA Cosmic COSV1010, ExAC rs766519356, gnomAD rs766519356, REVEL 0.12, AlphaMissense 0.17, Variant assessed as somatic; moderate impact.
- P24P (p.Pro24Pro), rs2131210981, gnomAD 9-5457098-C-A, CADD 7.73
- K25* (p.Lys25Ter), Ensembl rs2131210995
- K25E (p.Lys25Glu), Ensembl rs2131210995
- K25M (p.Lys25Met), ExAC rs754087767, TOPMed rs754087767, gnomAD rs754087767
- K25N (p.Lys25Asn), ExAC rs754998914, gnomAD rs754998914, SIFT 0.00
- K25R (p.Lys25Arg), ExAC rs754087767, TOPMed rs754087767, gnomAD rs754087767, REVEL 0.18, AlphaMissense 0.08
- K25K (p.Lys25Lys), rs754998914, gnomAD 9-5457101-G-A, CADD 8.37
- D26A (p.Asp26Ala), Ensembl rs2131211040
- D26E (p.Asp26Glu), Ensembl rs2131211048, REVEL 0.06, AlphaMissense 0.14
- D26G (p.Asp26Gly), Ensembl rs2131211040
- D26H (p.Asp26His), Ensembl rs2131211029
- D26N (p.Asp26Asn), Ensembl rs2131211029
- D26V (p.Asp26Val), Ensembl rs2131211040
- D26Y (p.Asp26Tyr), Ensembl rs2131211029, SIFT 0.01
- L27I (p.Leu27Ile), TOPMed rs1383983432, gnomAD rs1383983432, REVEL 0.14, AlphaMissense 0.07
- L27P (p.Leu27Pro), Ensembl rs2131211065
- L27Q (p.Leu27Gln), Ensembl rs2131211065
- L27R (p.Leu27Arg), Ensembl rs2131211065, SIFT 0.00
- L27L (p.Leu27Leu), rs1383983432, gnomAD 9-5457105-C-T, CADD 7.95
- Y28* (p.Tyr28Ter), Ensembl rs2131211102
- Y28C (p.Tyr28Cys), TOPMed rs1299227177, gnomAD rs1299227177
- Y28D (p.Tyr28Asp), Ensembl rs2131211084
- Y28F (p.Tyr28Phe), TOPMed rs1299227177, gnomAD rs1299227177, REVEL 0.09, AlphaMissense 0.12
- Y28H (p.Tyr28His), Ensembl rs2131211084, REVEL 0.08, AlphaMissense 0.23
- Y28N (p.Tyr28Asn), Ensembl rs2131211084, SIFT 0.00
- Y28Y (p.Tyr28Tyr), rs2131211102, gnomAD 9-5457110-T-C, CADD 5.90
- V29E (p.Val29Glu), Ensembl rs2131211119, REVEL 0.09, AlphaMissense 0.13
- V29L (p.Val29Leu), Ensembl rs2131211106
- V29M (p.Val29Met), Ensembl rs2131211106, SIFT 0.06
- V29V (p.Val29Val), rs2131211123, gnomAD 9-5457113-G-T, CADD 5.66
- V30A (p.Val30Ala), TOPMed rs1344190674, gnomAD rs1344190674, REVEL 0.14, AlphaMissense 0.13
- V30I (p.Val30Ile), gnomAD rs1819318390, REVEL 0.14, AlphaMissense 0.11
- V30L (p.Val30Leu), gnomAD rs1819318390, SIFT 0.00
- V30E (p.Val30Glu), gnomAD 9-5457115-T-A, REVEL 0.46, AlphaMissense 0.50
- V30V (p.Val30Val), rs753217395, gnomAD 9-5457116-A-G, CADD 7.19
- E31* (p.Glu31Ter), ESP rs373692552, ExAC rs373692552, TOPMed rs373692552, gnomAD rs373692552
- E31A (p.Glu31Ala), ExAC rs778185448, gnomAD rs778185448, REVEL 0.23, AlphaMissense 0.16
- E31D (p.Glu31Asp), TOPMed rs1242093213, gnomAD rs1242093213
- E31K (p.Glu31Lys), ESP rs373692552, ExAC rs373692552, TOPMed rs373692552, gnomAD rs373692552
- E31Q (p.Glu31Gln), ESP rs373692552, ExAC rs373692552, TOPMed rs373692552, gnomAD rs373692552, REVEL 0.13, AlphaMissense 0.12
- E31V (p.Glu31Val), ExAC rs778185448, gnomAD rs778185448, SIFT 0.02
- E31E (p.Glu31Glu), rs1242093213, gnomAD 9-5457119-G-A, CADD 1.82
- Y32C (p.Tyr32Cys), Ensembl rs2131211170, REVEL 0.27, AlphaMissense 0.47
- Y32D (p.Tyr32Asp), ExAC rs747317241, gnomAD rs747317241, REVEL 0.28, AlphaMissense 0.52
- Y32F (p.Tyr32Phe), Ensembl rs2131211170
- Y32H (p.Tyr32His), ExAC rs747317241, gnomAD rs747317241
- Y32N (p.Tyr32Asn), ExAC rs747317241, gnomAD rs747317241, SIFT 0.00
- G33A (p.Gly33Ala), Ensembl rs2131211195
- G33C (p.Gly33Cys), TOPMed rs1312762207, gnomAD rs1312762207
- G33D (p.Gly33Asp), Ensembl rs2131211195
- G33R (p.Gly33Arg), TOPMed rs1312762207, gnomAD rs1312762207
- G33S (p.Gly33Ser), TOPMed rs1312762207, gnomAD rs1312762207, REVEL 0.83, AlphaMissense 0.23
- G33V (p.Gly33Val), Ensembl rs2131211195, SIFT 0.00
- S34C (p.Ser34Cys), Ensembl rs2131211209
- S34G (p.Ser34Gly), Ensembl rs2131211209
- S34I (p.Ser34Ile), ESP rs140304675, ExAC rs140304675, TOPMed rs140304675, gnomAD rs140304675
- S34N (p.Ser34Asn), ESP rs140304675, ExAC rs140304675, TOPMed rs140304675, gnomAD rs140304675
- S34R (p.Ser34Arg), Ensembl rs2131211224, SIFT 0.00
- S34T (p.Ser34Thr), ESP rs140304675, ExAC rs140304675, TOPMed rs140304675, gnomAD rs140304675, REVEL 0.10, AlphaMissense 0.14
- N35H (p.Asn35His), Ensembl rs2131211236
- N35I (p.Asn35Ile), ExAC rs780953696, gnomAD rs780953696
- N35K (p.Asn35Lys), Ensembl rs2131211250
- N35T (p.Asn35Thr), ExAC rs780953696, gnomAD rs780953696, REVEL 0.20, AlphaMissense 0.20
- N35Y (p.Asn35Tyr), Ensembl rs2131211236, SIFT 0.00
- M36I (p.Met36Ile), Ensembl rs2131211266, REVEL 0.06, AlphaMissense 0.20
- M36K (p.Met36Lys), gnomAD rs1283319713, REVEL 0.27, AlphaMissense 0.55
- M36L (p.Met36Leu), Ensembl rs2131211256, REVEL 0.09, AlphaMissense 0.18
- M36T (p.Met36Thr), gnomAD rs1283319713, REVEL 0.11, AlphaMissense 0.29
- M36V (p.Met36Val), Ensembl rs2131211256, SIFT 1.00
- M36W (p.Met36Trp), gnomAD 9-5457121-A-ATGGT, CADD 23.30
- T37A (p.Thr37Ala), Ensembl rs1586763537
- T37I (p.Thr37Ile), gnomAD rs1314957482, REVEL 0.23, AlphaMissense 0.32
- T37K (p.Thr37Lys), gnomAD rs1314957482, REVEL 0.26, AlphaMissense 0.29
- T37R (p.Thr37Arg), gnomAD rs1314957482
- T37S (p.Thr37Ser), Ensembl rs1586763537, SIFT 0.00
- I38F (p.Ile38Phe), TOPMed rs1213866118, gnomAD rs1213866118
- I38M (p.Ile38Met), Ensembl rs1819319295
- I38N (p.Ile38Asn), gnomAD rs761826556
- I38S (p.Ile38Ser), gnomAD rs761826556, SIFT 0.00
- I38T (p.Ile38Thr), gnomAD rs761826556, REVEL 0.22, AlphaMissense 0.48
- I38V (p.Ile38Val), TOPMed rs1213866118, gnomAD rs1213866118, REVEL 0.02, AlphaMissense 0.09
- E39* (p.Glu39Ter), Ensembl rs2131211323
- E39D (p.Glu39Asp), Ensembl rs2131211338
- E39G (p.Glu39Gly), gnomAD rs1461816349, REVEL 0.34, AlphaMissense 0.23
- E39K (p.Glu39Lys), Ensembl rs2131211323
Public CD274 analysis runs
- CD274 analysis run — CD274 (1,340 variants) — completed 2026-08-19