PDCD1LG2 (Programmed cell death 1 ligand 2) variants and mutations
PDCD1LG2 (also known as Programmed cell death 1 ligand 2) is a human protein-coding gene encoding a programmed cell death 1 ligand 2 protein. By engaging PD-1, it suppresses T-cell receptor signaling and limits immune activation, particularly in antigen-presenting cells and selected tissues. Tumors can exploit this pathway for immune evasion, although its expression is generally more restricted than PD-L1. This analysis covers 1,349 PDCD1LG2 variants and mutations. Of these, 59% have computational variant effect predictions. Disease context includes melanoma, gastrointestinal stromal tumor, and prostate adenocarcinoma. Example PDCD1LG2 variants include I2F, I2L, and I2M.
Variant analysis overview
- Gene: PDCD1LG2
- Protein: Programmed cell death 1 ligand 2
- UniProt accession: Q9BQ51
- Organism: Homo sapiens
- Variants analyzed: 1349
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 1,188 unspecified-consequence records; 103 synonymous variants; 11 frameshift variants; 38 missense variants; 3 splice-region variants; 1 in-frame deletions; 4 stop-gained variants; 1 in-frame insertions
- Prediction scores: 801 variants have prediction scores (59% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: melanoma, gastrointestinal stromal tumor, prostate adenocarcinoma, lymphoid neoplasm, kidney neoplasm, breast ductal adenocarcinoma, hepatobiliary neoplasm, carcinoma of liver and intrahepatic biliary tract, bile duct carcinoma, HER2 positive breast carcinoma, ovarian endometrioid adenocarcinoma with squamous differentiation, myxedema.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 2 domains; 5 post-translational modification sites.
- Structural context: 1,044 variants have structural context.
- PTM context: 26 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 PDCD1LG2 variants
Examples include I2F, I2L, I2M, I2N, I2T, F3L, F3S, F3F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- I2F (p.Ile2Phe), Ensembl rs2129725791
- I2L (p.Ile2Leu), Ensembl rs2129725791, MetaLR 0.01, MetaSVM -0.95
- I2M (p.Ile2Met), Ensembl rs2129725821, REVEL 0.04, AlphaMissense 0.10
- I2N (p.Ile2Asn), ExAC rs764540241, TOPMed rs764540241, gnomAD rs764540241, REVEL 0.08, AlphaMissense 0.12, Uncertain significance, not specified
- I2T (p.Ile2Thr), ExAC rs764540241, TOPMed rs764540241, gnomAD rs764540241, REVEL 0.07, AlphaMissense 0.20, Uncertain significance
- F3L (p.Phe3Leu), gnomAD rs1229515001
- F3S (p.Phe3Ser), Ensembl rs2129725833, MetaLR 0.02, MetaSVM -0.97
- F3F (p.Phe3Phe), rs1229515001, gnomAD 9-5522555-C-T, CADD 9.73
- L4F (p.Leu4Phe), gnomAD rs1820295845, REVEL 0.12, AlphaMissense 0.07
- L4P (p.Leu4Pro), Ensembl rs990619741
- L4R (p.Leu4Arg), Ensembl rs990619741, REVEL 0.24, AlphaMissense 0.19
- L4V (p.Leu4Val), gnomAD rs1820295845, MetaLR 0.05, MetaSVM -1.05
- L5M (p.Leu5Met), NCI-TCGA Cosmic COSV6720, Ensembl rs2129725911, Variant assessed as somatic; moderate impact.
- L5P (p.Leu5Pro), Ensembl rs2129725935
- L5Q (p.Leu5Gln), Ensembl rs2129725935
- L5V (p.Leu5Val), Ensembl rs2129725911, MetaLR 0.05, MetaSVM -1.04
- L6R (p.Leu6Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L6V (p.Leu6Val), ESP rs370217715, ExAC rs370217715, TOPMed rs370217715, gnomAD rs370217715, MetaLR 0.02, MetaSVM -0.96
- L6L (p.Leu6Leu), rs370217715, gnomAD 9-5522562-C-T, CADD 7.72
- M7I (p.Met7Ile), Ensembl rs2129726017
- M7K (p.Met7Lys), ESP rs139799003, ExAC rs139799003, TOPMed rs139799003, gnomAD rs139799003, MetaLR 0.01, MetaSVM -0.95
- M7T (p.Met7Thr), ESP rs139799003, ExAC rs139799003, TOPMed rs139799003, gnomAD rs139799003, REVEL 0.02, AlphaMissense 0.14, Uncertain significance, not specified
- L8* (p.Leu8Ter), ExAC rs780669977, gnomAD rs780669977
- L8F (p.Leu8Phe), gnomAD rs1820296134
- L8S (p.Leu8Ser), ExAC rs780669977, gnomAD rs780669977, MetaLR 0.02, MetaSVM -1.03
- L8L (p.Leu8Leu), gnomAD 9-5522568-T-C, CADD 0.77
- S9C (p.Ser9Cys), Ensembl rs2129726100, MetaLR 0.04, MetaSVM -1.05
- S9R (p.Ser9Arg), TOPMed rs1820296181, REVEL 0.18, AlphaMissense 0.39
- L10M (p.Leu10Met), TOPMed rs1416485350, gnomAD rs1416485350, REVEL 0.10, AlphaMissense 0.10
- L10Q (p.Leu10Gln), Ensembl rs2129726167
- L10V (p.Leu10Val), TOPMed rs1416485350, gnomAD rs1416485350, MetaLR 0.04, MetaSVM -1.00
- L10L (p.Leu10Leu), rs2129726174, gnomAD 9-5522576-G-A, CADD 13.20
- E11* (p.Glu11Ter), Ensembl rs2129726225
- E11D (p.Glu11Asp), Ensembl rs2129726277
- E11K (p.Glu11Lys), Ensembl rs2129726225
- E11Q (p.Glu11Gln), Ensembl rs2129726225
- E11V (p.Glu11Val), Ensembl rs2129726262, MetaLR 0.01, MetaSVM -0.92
- E11N (p.Glu11Asn), rs567501802, gnomAD 9-5522575-TG-T, CADD 25.60
- E11E (p.Glu11Glu), gnomAD 9-5522579-A-G, CADD 5.80
- L12F (p.Leu12Phe), Ensembl rs2129726322
- L12L (p.Leu12Leu), rs770059253, gnomAD 9-5522580-T-C, CADD 2.27
- L12M (p.Leu12Met), gnomAD 9-5522580-T-A, REVEL 0.01, AlphaMissense 0.08
- Q13* (p.Gln13Ter), Ensembl rs2129726363, CADD 35.00
- Q13E (p.Gln13Glu), Ensembl rs2129726363
- Q13H (p.Gln13His), Ensembl rs2129726403
- Q13L (p.Gln13Leu), ExAC rs745559558, TOPMed rs745559558, gnomAD rs745559558, MetaLR 0.02, MetaSVM -0.98
- Q13R (p.Gln13Arg), ExAC rs745559558, TOPMed rs745559558, gnomAD rs745559558, REVEL 0.05, AlphaMissense 0.09
- L14H (p.Leu14His), Ensembl rs2129726452
- L14I (p.Leu14Ile), Ensembl rs2129726426
- L14P (p.Leu14Pro), Ensembl rs2129726452
- L14V (p.Leu14Val), Ensembl rs2129726426, MetaLR 0.04, MetaSVM -1.10
- H15D (p.His15Asp), Ensembl rs2129726500
- H15Q (p.His15Gln), ExAC rs755559932, TOPMed rs755559932, gnomAD rs755559932
- H15Y (p.His15Tyr), Ensembl rs2129726500, MetaLR 0.03, MetaSVM -0.92
- H15H (p.His15His), rs755559932, gnomAD 9-5522591-C-T, CADD 0.20
- Q16H (p.Gln16His), Ensembl rs2129726560
- Q16R (p.Gln16Arg), Ensembl rs2129726545, MetaLR 0.01, MetaSVM -0.96
- I17K (p.Ile17Lys), TOPMed rs941236320, gnomAD rs941236320
- I17L (p.Ile17Leu), Ensembl rs2129726581, MetaLR 0.01, MetaSVM -0.96
- I17R (p.Ile17Arg), TOPMed rs941236320, gnomAD rs941236320, REVEL 0.02, AlphaMissense 0.10
- I17T (p.Ile17Thr), TOPMed rs941236320, gnomAD rs941236320, REVEL 0.02, AlphaMissense 0.05
- I17V (p.Ile17Val), gnomAD 9-5522595-A-G, REVEL 0.01, AlphaMissense 0.08
- I17M (p.Ile17Met), gnomAD 9-5522597-A-G, REVEL 0.03, AlphaMissense 0.07
- A18E (p.Ala18Glu), ExAC rs779657826, TOPMed rs779657826, gnomAD rs779657826, REVEL 0.03, AlphaMissense 0.23, Uncertain significance
- A18G (p.Ala18Gly), ExAC rs779657826, TOPMed rs779657826, gnomAD rs779657826, MetaLR 0.03, MetaSVM -1.01, Uncertain significance
- A18P (p.Ala18Pro), rs1037381642, ClinGen CA188299559, ClinVar RCV004272242, TOPMed rs1037381642, REVEL 0.07, AlphaMissense 0.14, Uncertain significance, not specified
- A18V (p.Ala18Val), rs779657826, ClinGen CA4973825, ClinVar RCV004502964, ExAC rs779657826, REVEL 0.05, AlphaMissense 0.20, Uncertain significance, not specified
- A19G (p.Ala19Gly), TOPMed rs1820547018
- A19P (p.Ala19Pro), Ensembl rs1820296746, MetaLR 0.06, MetaSVM -1.02
- A19T (p.Ala19Thr), Ensembl rs1820296746, REVEL 0.12, AlphaMissense 0.33
- A19V (p.Ala19Val), gnomAD 9-5534745-C-T, REVEL 0.14, AlphaMissense 0.39
- A19A (p.Ala19Ala), gnomAD 9-5534746-T-C, CADD 16.20
- L20* (p.Leu20Ter), ExAC rs778770992, gnomAD rs778770992
- L20F (p.Leu20Phe), Ensembl rs1820547180
- L20S (p.Leu20Ser), ExAC rs778770992, gnomAD rs778770992, MetaLR 0.02, MetaSVM -1.01
- L20V (p.Leu20Val), TOPMed rs1820547052, REVEL 0.08, AlphaMissense 0.11
- L20L (p.Leu20Leu), rs1820547180, gnomAD 9-5534749-A-G, CADD 7.29
- F21C (p.Phe21Cys), Ensembl rs2129791886, REVEL 0.27, AlphaMissense 0.92
- F21I (p.Phe21Ile), Ensembl rs2129791872
- F21L (p.Phe21Leu), Ensembl rs2129791908
- F21S (p.Phe21Ser), Ensembl rs2129791886
- F21Y (p.Phe21Tyr), Ensembl rs2129791886, MetaLR 0.04, MetaSVM -1.17
- T22A (p.Thr22Ala), TOPMed rs768189989, gnomAD rs768189989, REVEL 0.17, AlphaMissense 0.16
- T22I (p.Thr22Ile), TOPMed rs1820547275
- T22K (p.Thr22Lys), NCI-TCGA Cosmic COSV6720, Variant assessed as somatic; moderate impact.
- T22R (p.Thr22Arg), TOPMed rs1820547275
- T22S (p.Thr22Ser), TOPMed rs768189989, gnomAD rs768189989, MetaLR 0.02, MetaSVM -1.07
- T22T (p.Thr22Thr), gnomAD 9-5534755-A-G, CADD 6.16
- V23L (p.Val23Leu), TOPMed rs1416367564
- V23M (p.Val23Met), TOPMed rs1416367564, MetaLR 0.05, MetaSVM -1.15
- V23E (p.Val23Glu), gnomAD 9-5534757-T-A, REVEL 0.34, AlphaMissense 0.91
- V23V (p.Val23Val), rs2129791987, gnomAD 9-5534758-G-A, CADD 7.13
- T24A (p.Thr24Ala), Ensembl rs2129792002
- T24I (p.Thr24Ile), TOPMed rs1320163307, gnomAD rs1320163307, REVEL 0.07, AlphaMissense 0.18
- T24R (p.Thr24Arg), TOPMed rs1320163307, gnomAD rs1320163307
- T24S (p.Thr24Ser), Ensembl rs2129792002, MetaLR 0.03, MetaSVM -1.02
- T24T (p.Thr24Thr), rs754474232, gnomAD 9-5534761-A-G, CADD 2.67
- V25A (p.Val25Ala), TOPMed rs1820547494
- V25D (p.Val25Asp), TOPMed rs1820547494
- V25G (p.Val25Gly), TOPMed rs1820547494
- V25I (p.Val25Ile), 1000Genomes rs117136501, ExAC rs117136501, gnomAD rs117136501, REVEL 0.03, AlphaMissense 0.11
- V25L (p.Val25Leu), 1000Genomes rs117136501, ExAC rs117136501, gnomAD rs117136501, MetaLR 0.02, MetaSVM -1.01
- V25V (p.Val25Val), rs941757574, gnomAD 9-5534764-C-T, CADD 8.04
- P26H (p.Pro26His), Ensembl rs2129792116
- P26L (p.Pro26Leu), Ensembl rs2129792116
- P26R (p.Pro26Arg), Ensembl rs2129792116, MetaLR 0.05, MetaSVM -1.16
- K27* (p.Lys27Ter), Ensembl rs2129792148
- K27E (p.Lys27Glu), Ensembl rs2129792148
- K27M (p.Lys27Met), ExAC rs777689711, TOPMed rs777689711, gnomAD rs777689711, MetaLR 0.03, MetaSVM -1.06
- K27N (p.Lys27Asn), Ensembl rs2129792176, REVEL 0.05, AlphaMissense 0.55
- K27R (p.Lys27Arg), ExAC rs777689711, TOPMed rs777689711, gnomAD rs777689711, REVEL 0.07, AlphaMissense 0.09
- E28* (p.Glu28Ter), 1000Genomes rs150821059, ExAC rs150821059, gnomAD rs150821059, CADD 35.00
- E28D (p.Glu28Asp), ExAC rs770000726, gnomAD rs770000726, REVEL 0.06, AlphaMissense 0.14
- E28K (p.Glu28Lys), 1000Genomes rs150821059, ExAC rs150821059, gnomAD rs150821059
- E28Q (p.Glu28Gln), 1000Genomes rs150821059, ExAC rs150821059, gnomAD rs150821059
- E28V (p.Glu28Val), Ensembl rs2129792206, MetaLR 0.02, MetaSVM -1.05
- L29M (p.Leu29Met), Ensembl rs1586802925
- L29P (p.Leu29Pro), Ensembl rs2129792271
- L29Q (p.Leu29Gln), Ensembl rs2129792271
- L29V (p.Leu29Val), Ensembl rs1586802925, MetaLR 0.01, MetaSVM -0.92
- Y30* (p.Tyr30Ter), ExAC rs775859590, gnomAD rs775859590, CADD 33.00
- Y30C (p.Tyr30Cys), Ensembl rs2129792333
- Y30D (p.Tyr30Asp), Ensembl rs1586802928
- Y30F (p.Tyr30Phe), Ensembl rs2129792333
- Y30H (p.Tyr30His), Ensembl rs1586802928, REVEL 0.27, AlphaMissense 0.29
- Y30N (p.Tyr30Asn), Ensembl rs1586802928, MetaLR 0.04, MetaSVM -1.09
- Y30Y (p.Tyr30Tyr), rs775859590, gnomAD 9-5534779-C-T, CADD 4.41
- I31L (p.Ile31Leu), gnomAD rs1411122146, REVEL 0.01, AlphaMissense 0.10
- I31V (p.Ile31Val), gnomAD 9-5534780-A-G, REVEL 0.01, AlphaMissense 0.07
- I31T (p.Ile31Thr), gnomAD 9-5534781-T-C, REVEL 0.01, AlphaMissense 0.08
- I32L (p.Ile32Leu), Ensembl rs2129792400
- I32M (p.Ile32Met), Ensembl rs2129792428, MetaLR 0.02, MetaSVM -1.05
- I32R (p.Ile32Arg), ESP rs369302753, ExAC rs369302753, TOPMed rs369302753, gnomAD rs369302753, REVEL 0.09, AlphaMissense 0.21
- I32T (p.Ile32Thr), ESP rs369302753, ExAC rs369302753, TOPMed rs369302753, gnomAD rs369302753, REVEL 0.05, AlphaMissense 0.06
- E33* (p.Glu33Ter), ESP rs373326879, ExAC rs373326879, gnomAD rs373326879
- E33D (p.Glu33Asp), TOPMed rs1820548093, REVEL 0.04, AlphaMissense 0.09
- E33G (p.Glu33Gly), Ensembl rs2129792458
- E33K (p.Glu33Lys), ESP rs373326879, ExAC rs373326879, gnomAD rs373326879, REVEL 0.06, AlphaMissense 0.22
- E33Q (p.Glu33Gln), ESP rs373326879, ExAC rs373326879, gnomAD rs373326879, REVEL 0.07, AlphaMissense 0.18
- E33V (p.Glu33Val), Ensembl rs2129792458, MetaLR 0.05, MetaSVM -1.04
- H34D (p.His34Asp), ExAC rs774978243, gnomAD rs774978243
- H34L (p.His34Leu), Ensembl rs1820548187
- H34N (p.His34Asn), ExAC rs774978243, gnomAD rs774978243
- H34P (p.His34Pro), Ensembl rs1820548187, MetaLR 0.04, MetaSVM -1.04
- H34Q (p.His34Gln), gnomAD rs1820548258, REVEL 0.09, AlphaMissense 0.21
- H34R (p.His34Arg), Ensembl rs1820548187, REVEL 0.09, AlphaMissense 0.12
- H34Y (p.His34Tyr), ExAC rs774978243, gnomAD rs774978243, REVEL 0.03, AlphaMissense 0.06
- G35A (p.Gly35Ala), Ensembl rs1820548308, REVEL 0.17, AlphaMissense 0.36
- G35D (p.Gly35Asp), Ensembl rs1820548308
- G35R (p.Gly35Arg), Ensembl rs2129792538
- G35S (p.Gly35Ser), Ensembl rs2129792538, REVEL 0.14, AlphaMissense 0.19
- G35V (p.Gly35Val), Ensembl rs1820548308, MetaLR 0.10, MetaSVM -0.98
- S36C (p.Ser36Cys), Ensembl rs2129792582, MetaLR 0.04, MetaSVM -1.08
- S36R (p.Ser36Arg), TOPMed rs992575112, gnomAD rs992575112, REVEL 0.16, AlphaMissense 0.35
- S36N (p.Ser36Asn), gnomAD 9-5534796-G-A, REVEL 0.17, AlphaMissense 0.13
- N37D (p.Asn37Asp), Ensembl rs2129792615
- N37I (p.Asn37Ile), Ensembl rs2129792628
- N37K (p.Asn37Lys), ESP rs376297615, TOPMed rs376297615, gnomAD rs376297615, REVEL 0.09, AlphaMissense 0.50
- N37S (p.Asn37Ser), Ensembl rs2129792628, REVEL 0.13, AlphaMissense 0.09
- N37Y (p.Asn37Tyr), Ensembl rs2129792615, MetaLR 0.03, MetaSVM -1.09
- N37N (p.Asn37Asn), rs376297615, gnomAD 9-5534800-T-C, CADD 7.70
- V38E (p.Val38Glu), Ensembl rs2129792670
- V38G (p.Val38Gly), Ensembl rs2129792670
- V38L (p.Val38Leu), Ensembl rs2129792657, MetaLR 0.05, MetaSVM -1.06
- V38M (p.Val38Met), Ensembl rs2129792657, REVEL 0.23, AlphaMissense 0.31
- T39A (p.Thr39Ala), Ensembl rs2129792699
- T39I (p.Thr39Ile), Ensembl rs2129792716
- T39N (p.Thr39Asn), Ensembl rs2129792716
- T39P (p.Thr39Pro), Ensembl rs2129792699
- T39S (p.Thr39Ser), Ensembl rs2129792716, NCI-TCGA Cosmic COSV1011, MetaLR 0.04, MetaSVM -1.08, Variant assessed as somatic; moderate impact.
- T39T (p.Thr39Thr), rs2129792727, gnomAD 9-5534806-C-G, CADD 7.56
- L40M (p.Leu40Met), Ensembl rs2129792746
- L40P (p.Leu40Pro), gnomAD rs1406771137, REVEL 0.41, AlphaMissense 0.94
- L40V (p.Leu40Val), Ensembl rs2129792746, MetaLR 0.05, MetaSVM -1.01, Uncertain significance, not specified
- L40L (p.Leu40Leu), rs1446952147, gnomAD 9-5534809-G-A, CADD 8.29
- E41* (p.Glu41Ter), Ensembl rs2129792791
- E41D (p.Glu41Asp), ExAC rs762452068, gnomAD rs762452068, REVEL 0.24, AlphaMissense 0.45
- E41K (p.Glu41Lys), Ensembl rs2129792791
- E41Q (p.Glu41Gln), Ensembl rs2129792791
- E41V (p.Glu41Val), Ensembl rs2129792812, MetaLR 0.10, MetaSVM -1.04
Public PDCD1LG2 analysis runs
- PDCD1LG2 analysis run — PDCD1LG2 (1,349 variants) — completed 2026-08-20