LAG3 (P18627) variants and mutations
LAG3 (also known as P18627) is a human protein-coding gene encoding a lymphocyte activation gene 3 protein. It restrains activated and chronically stimulated T cells and contributes to immune tolerance and T-cell exhaustion. Its coexpression with other inhibitory receptors in tumors makes LAG-3 an established immune-checkpoint target in cancer therapy. This analysis covers 925 LAG3 variants and mutations. Of these, 84% have computational variant effect predictions. Disease context includes melanoma, non-small cell lung carcinoma, and colorectal cancer. Example LAG3 variants include W2R, W2C, and E3E.
Variant analysis overview
- Gene: LAG3
- Protein: P18627
- UniProt accession: P18627
- Organism: Homo sapiens
- Variants analyzed: 925
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 671 unspecified-consequence records; 153 missense variants; 74 synonymous variants; 5 stop-gained variants; 2 in-frame deletions; 1 splice-region variants; 18 frameshift variants; 1 in-frame insertions; 2 substitution
- Prediction scores: 776 variants have prediction scores (84% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: melanoma, non-small cell lung carcinoma, colorectal cancer, metastatic colorectal cancer, gastric cancer, breast cancer, head and neck squamous cell carcinoma, gastroesophageal junction adenocarcinoma, urinary bladder carcinoma, gastric neoplasm, cancer, diffuse large B-cell lymphoma.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 4 domains; 4 post-translational modification sites.
- Structural context: 720 variants have structural context.
- PTM context: 5 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 LAG3 variants
Examples include W2R, W2C, E3E, A4A, Q5E, Q5*, F6L, L7L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- W2R (p.Trp2Arg), gnomAD 12-6772856-T-C, REVEL 0.03, CADD 8.93
- W2C (p.Trp2Cys), gnomAD 12-6772858-G-C, REVEL 0.06, CADD 24.70
- E3E (p.Glu3Glu), rs1157069952, gnomAD 12-6772861-G-A, CADD 10.40
- A4A (p.Ala4Ala), gnomAD 12-6772864-T-G, CADD 10.90
- Q5E (p.Gln5Glu), gnomAD 12-6772865-C-G, REVEL 0.02, CADD 13.60
- Q5* (p.Gln5Ter), gnomAD 12-6772865-C-T, CADD 33.00
- F6L (p.Phe6Leu), Ensembl rs1592494908
- L7L (p.Leu7Leu), rs780079087, gnomAD 12-6772873-G-C, CADD 8.20
- G8S (p.Gly8Ser), TOPMed rs1941859458, gnomAD rs1941859458, REVEL 0.08, CADD 21.70
- G8D (p.Gly8Asp), gnomAD 12-6772875-G-A, REVEL 0.01, CADD 17.90
- G8G (p.Gly8Gly), gnomAD 12-6772876-C-T, CADD 11.90
- L9F (p.Leu9Phe), gnomAD 12-6772879-G-T, REVEL 0.01, CADD 11.60
- F11C (p.Phe11Cys), NCI-TCGA Cosmic COSV9917, cosmic curated COSV99179, Variant assessed as somatic; moderate impact.
- F11L (p.Phe11Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L12L (p.Leu12Leu), rs984828883, gnomAD 12-6772886-C-T, CADD 12.70
- Q13H (p.Gln13His), gnomAD rs1322282282, REVEL 0.06, CADD 2.88
- Q13K (p.Gln13Lys), gnomAD 12-6772889-C-A, REVEL 0.07, CADD 15.50
- Q13P (p.Gln13Pro), gnomAD 12-6772890-A-C, REVEL 0.08, CADD 12.00
- P14L (p.Pro14Leu), TOPMed rs1014999225, gnomAD rs1014999225, REVEL 0.03, CADD 3.96
- P14Q (p.Pro14Gln), TOPMed rs1014999225, gnomAD rs1014999225
- P14A (p.Pro14Ala), gnomAD 12-6772892-C-G, REVEL 0.03, CADD 11.30
- P14P (p.Pro14Pro), rs746963580, gnomAD 12-6772894-G-A, CADD 8.31
- L15F (p.Leu15Phe), gnomAD 12-6772895-C-T, REVEL 0.08, CADD 23.50
- L15R (p.Leu15Arg), gnomAD 12-6772896-T-G, REVEL 0.24, CADD 21.20
- W16L (p.Trp16Leu), cosmic curated COSV99179, Ensembl rs976491768, REVEL 0.11, CADD 23.50
- V17A (p.Val17Ala), gnomAD rs1941859729, REVEL 0.03, CADD 4.94
- V17L (p.Val17Leu), TOPMed rs951729345
- V17M (p.Val17Met), gnomAD 12-6772901-G-A, REVEL 0.06, CADD 20.50
- A18T (p.Ala18Thr), Ensembl rs1252644199, REVEL 0.02, CADD 22.70
- P19L (p.Pro19Leu), cosmic curated COSV10722, NCI-TCGA TCGA novel, REVEL 0.07, CADD 26.20, Variant assessed as somatic; moderate impact.
- P19S (p.Pro19Ser), ExAC rs768527438, gnomAD rs768527438, REVEL 0.07, CADD 20.50
- V20A (p.Val20Ala), gnomAD 12-6773192-T-C, REVEL 0.02, CADD 13.80
- K21R (p.Lys21Arg), Ensembl rs1941862456
- K21K (p.Lys21Lys), rs769148979, gnomAD 12-6773196-G-A, CADD 8.47
- P22R (p.Pro22Arg), TOPMed rs1941862507, REVEL 0.04, CADD 17.60
- P22L (p.Pro22Leu), gnomAD 12-6773198-C-T, REVEL 0.05, CADD 18.50
- P22P (p.Pro22Pro), rs1370673375, gnomAD 12-6773199-T-G, CADD 5.43
- L23F (p.Leu23Phe), TOPMed rs1393242900, REVEL 0.02, CADD 13.70
- P25S (p.Pro25Ser), cosmic curated COSV52568, 1000Genomes rs146038483, ESP rs146038483, ExAC rs146038483, REVEL 0.05, CADD 11.10
- P25P (p.Pro25Pro), gnomAD 12-6773208-A-G, CADD 3.62
- G26R (p.Gly26Arg), NCI-TCGA Cosmic COSV9918, cosmic curated COSV99180, Variant assessed as somatic; moderate impact.
- G26G (p.Gly26Gly), rs1941862599, gnomAD 12-6773211-G-A, CADD 7.36
- A27D (p.Ala27Asp), TOPMed rs1941862629
- A27T (p.Ala27Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E28Q (p.Glu28Gln), Ensembl rs1941862691, REVEL 0.03, CADD 16.70
- V29V (p.Val29Val), rs1280990927, gnomAD 12-6773220-C-T, CADD 5.91
- P30A (p.Pro30Ala), ExAC rs762024185, TOPMed rs762024185, gnomAD rs762024185, REVEL 0.01, CADD 0.39, Uncertain significance, not specified
- P30L (p.Pro30Leu), cosmic curated COSV52568, ESP rs369567695, ExAC rs369567695, TOPMed rs369567695, REVEL 0.02, CADD 4.86, Uncertain significance
- P30R (p.Pro30Arg), rs369567695, ClinGen CA6415174, ClinVar RCV004407178, ESP rs369567695, REVEL 0.01, CADD 4.85, Uncertain significance, not specified
- P30S (p.Pro30Ser), ExAC rs762024185, TOPMed rs762024185, gnomAD rs762024185, Uncertain significance
- P30P (p.Pro30Pro), gnomAD 12-6773223-G-C, CADD 1.26
- V31M (p.Val31Met), gnomAD 12-6773224-G-A, REVEL 0.07, CADD 18.70
- W33* (p.Trp33Ter), NCI-TCGA Cosmic COSV9917, cosmic curated COSV99179, CADD 37.00, Variant assessed as somatic; high impact.
- W33C (p.Trp33Cys), NCI-TCGA Cosmic COSV5256, REVEL 0.23, CADD 28.90, Variant assessed as somatic; moderate impact.
- A34S (p.Ala34Ser), ExAC rs766752202, TOPMed rs766752202, gnomAD rs766752202, REVEL 0.12, CADD 26.30
- A34T (p.Ala34Thr), ExAC rs766752202, TOPMed rs766752202, gnomAD rs766752202, REVEL 0.14, CADD 27.30
- A34V (p.Ala34Val), gnomAD 12-6773234-C-T, REVEL 0.05, CADD 22.90
- Q35* (p.Gln35Ter), gnomAD rs1203070818
- Q35K (p.Gln35Lys), gnomAD 12-6773236-C-A, REVEL 0.03, CADD 20.70
- Q35Q (p.Gln35Gln), gnomAD 12-6773238-G-A, CADD 13.00
- E36G (p.Glu36Gly), gnomAD 12-6773240-A-G, REVEL 0.12, CADD 32.00
- E36D (p.Glu36Asp), gnomAD 12-6773241-G-C, REVEL 0.08, CADD 23.30
- G37E (p.Gly37Glu), NCI-TCGA Cosmic COSV5257, cosmic curated COSV52570, Variant assessed as somatic; moderate impact.
- G37W (p.Gly37Trp), Ensembl rs1941862901, REVEL 0.33, CADD 29.60
- G37G (p.Gly37Gly), rs976081703, gnomAD 12-6773244-G-A, CADD 11.10
- A38S (p.Ala38Ser), rs751673910, NCI-TCGA Cosmic COSV9917, cosmic curated COSV99179, ExAC rs751673910, REVEL 0.07, CADD 18.20, Variant assessed as somatic; moderate impact.
- A38T (p.Ala38Thr), ExAC rs751673910, gnomAD rs751673910, REVEL 0.05, CADD 23.00
- A38V (p.Ala38Val), NCI-TCGA TCGA novel, REVEL 0.02, CADD 20.90, Variant assessed as somatic; moderate impact.
- A38P (p.Ala38Pro), gnomAD 12-6773245-G-C, REVEL 0.09, CADD 24.40
- P39T (p.Pro39Thr), TOPMed rs1941862981
- P39P (p.Pro39Pro), rs755173480, gnomAD 12-6773250-T-C, CADD 11.40
- A40V (p.Ala40Val), NCI-TCGA Cosmic COSV9917, cosmic curated COSV99179, Variant assessed as somatic; moderate impact.
- A40A (p.Ala40Ala), gnomAD 12-6773253-C-T, CADD 13.10
- Q41* (p.Gln41Ter), TOPMed rs1267114843, gnomAD rs1267114843
- Q41E (p.Gln41Glu), TOPMed rs1267114843, gnomAD rs1267114843, REVEL 0.06, CADD 17.60
- Q41R (p.Gln41Arg), TOPMed rs1250686307, gnomAD rs1250686307, REVEL 0.03, CADD 15.70
- Q41H (p.Gln41His), gnomAD 12-6773256-G-C, REVEL 0.04, CADD 14.70
- L42L (p.Leu42Leu), rs1176260495, gnomAD 12-6773259-C-T, CADD 11.30
- P43A (p.Pro43Ala), cosmic curated COSV52568, 1000Genomes rs781221749, ExAC rs781221749, gnomAD rs781221749, REVEL 0.18, CADD 25.10
- P43S (p.Pro43Ser), 1000Genomes rs781221749, ExAC rs781221749, gnomAD rs781221749, REVEL 0.15, CADD 25.90
- P43L (p.Pro43Leu), gnomAD 12-6773261-C-T, REVEL 0.25, CADD 26.60
- P43P (p.Pro43Pro), rs1941863170, gnomAD 12-6773262-C-T, CADD 13.90
- C44W (p.Cys44Trp), TOPMed rs1941863286, gnomAD rs1941863286, REVEL 0.47, CADD 25.70
- C44Y (p.Cys44Tyr), ExAC rs752704799, gnomAD rs752704799, REVEL 0.47, CADD 28.20
- C44C (p.Cys44Cys), gnomAD 12-6773265-C-T, CADD 14.80
- S45G (p.Ser45Gly), rs533786810, ClinGen CA6415182, cosmic curated COSV10506, ClinVar RCV004407167, REVEL 0.02, CADD 23.10, Uncertain significance, not specified
- S45N (p.Ser45Asn), gnomAD 12-6773267-G-A, REVEL 0.03, CADD 18.10
- S45I (p.Ser45Ile), gnomAD 12-6773267-G-T, REVEL 0.03, CADD 18.80
- S45S (p.Ser45Ser), rs1426479257, gnomAD 12-6773268-C-T, CADD 12.00
- P46L (p.Pro46Leu), ExAC rs777597742, TOPMed rs777597742, gnomAD rs777597742, REVEL 0.02, CADD 18.20
- P46S (p.Pro46Ser), TOPMed rs1941863378, REVEL 0.05, CADD 22.50
- P46P (p.Pro46Pro), rs749087540, gnomAD 12-6773271-C-T, CADD 14.00
- T47R (p.Thr47Arg), Ensembl rs2137805600
- p.Thr47 Gln51delinsLys, rs773617171, gnomAD 12-6773272-ACAATC, CADD 14.80
- T47I (p.Thr47Ile), gnomAD 12-6773273-C-T, REVEL 0.04, CADD 18.60
- T47T (p.Thr47Thr), gnomAD 12-6773274-A-G, CADD 11.30
- I48T (p.Ile48Thr), ExAC rs770557883, gnomAD rs770557883, REVEL 0.01, CADD 6.26
- I48V (p.Ile48Val), gnomAD 12-6773275-A-G, REVEL 0.02, CADD 11.00
- I48I (p.Ile48Ile), gnomAD 12-6773277-C-T, CADD 9.71
- I48M (p.Ile48Met), gnomAD 12-6773277-C-G, REVEL 0.04, CADD 15.80
- P49T (p.Pro49Thr), TOPMed rs953432394, gnomAD rs953432394, REVEL 0.03, CADD 16.60
- P49P (p.Pro49Pro), rs778605598, gnomAD 12-6773280-C-T, CADD 10.10
- L50I (p.Leu50Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L50L (p.Leu50Leu), rs745318168, gnomAD 12-6773283-C-G, CADD 7.82
- Q51R (p.Gln51Arg), ExAC rs771582084, gnomAD rs771582084, REVEL 0.03, CADD 10.60
- Q51Q (p.Gln51Gln), rs1213115128, gnomAD 12-6773286-G-A, CADD 8.38
- D52N (p.Asp52Asn), gnomAD 12-6773287-G-A, REVEL 0.03, CADD 17.10
- D52D (p.Asp52Asp), rs1297512789, gnomAD 12-6773289-T-C, CADD 7.81
- L53L (p.Leu53Leu), rs1343489128, gnomAD 12-6773292-C-T, CADD 8.88
- S54G (p.Ser54Gly), gnomAD 12-6773293-A-G, REVEL 0.02, CADD 14.90
- S54N (p.Ser54Asn), gnomAD 12-6773294-G-A, REVEL 0.04, CADD 14.10
- S54S (p.Ser54Ser), rs1230775185, gnomAD 12-6773295-C-T, CADD 9.38
- L55F (p.Leu55Phe), gnomAD 12-6773296-C-T, REVEL 0.02, CADD 16.20
- R57* (p.Arg57Ter), NCI-TCGA Cosmic COSV5256, cosmic curated COSV52566, Variant assessed as somatic; high impact.
- R57Q (p.Arg57Gln), NCI-TCGA TCGA novel, TOPMed rs1941863994, REVEL 0.05, CADD 22.70, Variant assessed as somatic; moderate impact.
- R57R (p.Arg57Arg), gnomAD 12-6773302-C-A, CADD 11.00
- R58T (p.Arg58Thr), TOPMed rs1264184775, gnomAD rs1264184775, REVEL 0.07, CADD 13.70
- R58R (p.Arg58Arg), rs776952112, gnomAD 12-6773307-A-G, CADD 14.60
- A59S (p.Ala59Ser), Ensembl rs1941864097
- A59T (p.Ala59Thr), gnomAD 12-6773308-G-A, REVEL 0.03, CADD 14.40
- A59V (p.Ala59Val), gnomAD 12-6773309-C-T, REVEL 0.01, CADD 13.50
- A59A (p.Ala59Ala), gnomAD 12-6773310-A-G, CADD 13.60
- G60R (p.Gly60Arg), ExAC rs762413506, TOPMed rs762413506, gnomAD rs762413506, REVEL 0.05, CADD 15.70
- V61I (p.Val61Ile), ExAC rs770243423, TOPMed rs770243423, gnomAD rs770243423, REVEL 0.05, CADD 18.60, Uncertain significance, not specified
- V61A (p.Val61Ala), gnomAD 12-6773315-T-C, REVEL 0.07, CADD 23.90
- T62I (p.Thr62Ile), TOPMed rs1941864223, gnomAD rs1941864223, REVEL 0.03, CADD 14.30, Uncertain significance, not specified
- T62S (p.Thr62Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q64L (p.Gln64Leu), TOPMed rs1941864269, REVEL 0.06, CADD 23.30
- Q64R (p.Gln64Arg), TOPMed rs1941864269
- Q64* (p.Gln64Ter), gnomAD 12-6773323-C-T, CADD 36.00
- P67S (p.Pro67Ser), ESP rs149722682, ExAC rs149722682, TOPMed rs149722682, gnomAD rs149722682, REVEL 0.06, CADD 23.80
- P67T (p.Pro67Thr), ESP rs149722682, ExAC rs149722682, TOPMed rs149722682, gnomAD rs149722682, REVEL 0.05, CADD 23.30
- P67P (p.Pro67Pro), rs766701097, gnomAD 12-6773334-A-C, CADD 14.00
- D68E (p.Asp68Glu), TOPMed rs1941864502, gnomAD rs1941864502, REVEL 0.02, CADD 20.70
- D68N (p.Asp68Asn), Ensembl rs1941864458, REVEL 0.09, CADD 24.60
- D68G (p.Asp68Gly), gnomAD 12-6773336-A-G, REVEL 0.06, CADD 23.80
- S69G (p.Ser69Gly), gnomAD rs1187624530, REVEL 0.03, CADD 24.50
- S69N (p.Ser69Asn), ExAC rs751833193
- S69R (p.Ser69Arg), gnomAD 12-6773697-T-A, REVEL 0.01, CADD 0.45
- S69S (p.Ser69Ser), gnomAD 12-6773697-T-C, CADD 1.86
- G70S (p.Gly70Ser), gnomAD rs1158947650, REVEL 0.03, CADD 16.30
- G70V (p.Gly70Val), ExAC rs770317583, gnomAD rs770317583, REVEL 0.01, CADD 3.26
- G70C (p.Gly70Cys), gnomAD 12-6773698-G-T, REVEL 0.06, CADD 18.60
- G70D (p.Gly70Asp), gnomAD 12-6773699-G-A, REVEL 0.01, CADD 3.43
- G70G (p.Gly70Gly), gnomAD 12-6773700-C-A, CADD 6.75
- P71L (p.Pro71Leu), ExAC rs749595028, gnomAD rs749595028, REVEL 0.03, CADD 16.80
- P71S (p.Pro71Ser), cosmic curated COSV52566, Ensembl rs1941869088, REVEL 0.09, CADD 14.20
- P71A (p.Pro71Ala), gnomAD 12-6773701-C-G, REVEL 0.07, CADD 13.70
- P71T (p.Pro71Thr), gnomAD 12-6773701-C-A, REVEL 0.07, CADD 14.20
- P71R (p.Pro71Arg), gnomAD 12-6773702-C-G, REVEL 0.02, CADD 12.80
- P71Q (p.Pro71Gln), gnomAD 12-6773702-C-A, REVEL 0.01, CADD 11.50
- P71P (p.Pro71Pro), rs1168998080, gnomAD 12-6773703-G-A, CADD 4.07
- P72T (p.Pro72Thr), ExAC rs771448332, TOPMed rs771448332, gnomAD rs771448332, REVEL 0.02, CADD 9.76
- P72S (p.Pro72Ser), gnomAD 12-6773704-C-T, REVEL 0.01, CADD 10.40
- P72L (p.Pro72Leu), gnomAD 12-6773705-C-T, REVEL 0.05, CADD 17.90
- P72H (p.Pro72His), gnomAD 12-6773705-C-A, REVEL 0.09, CADD 21.90
- p.Pro72 Ala73insLeuHis, gnomAD 12-6773705-C-CGCT, CADD 11.50
- P72R (p.Pro72Arg), gnomAD 12-6773705-C-G, REVEL 0.04, CADD 18.10
- P72P (p.Pro72Pro), gnomAD 12-6773706-C-G, CADD 1.86
- A73T (p.Ala73Thr), TOPMed rs1941869293, gnomAD rs1941869293, REVEL 0.01, CADD 11.20
- A73L (p.Ala73Leu), gnomAD 12-6773699-GCCCGC, CADD 24.00
- A73P (p.Ala73Pro), gnomAD 12-6773707-G-C, REVEL 0.04, CADD 18.20
- A73S (p.Ala73Ser), gnomAD 12-6773707-G-T, REVEL 0.02, CADD 9.48
- A73G (p.Ala73Gly), gnomAD 12-6773708-C-G, REVEL 0.01, CADD 8.19
- A73D (p.Ala73Asp), gnomAD 12-6773708-C-A, REVEL 0.01, CADD 10.30
- A73V (p.Ala73Val), gnomAD 12-6773708-C-T, REVEL 0.01, CADD 10.30
- A73A (p.Ala73Ala), gnomAD 12-6773709-T-C, CADD 5.28
- A74P (p.Ala74Pro), Ensembl rs2137806159
- A74V (p.Ala74Val), gnomAD rs1941869321, REVEL 0.03, CADD 11.90
- A74R (p.Ala74Arg), rs1941869032, gnomAD 12-6773698-G-GGCC, CADD 20.90
- A74T (p.Ala74Thr), gnomAD 12-6773710-G-A, REVEL 0.01, CADD 6.96
- A74S (p.Ala74Ser), gnomAD 12-6773710-G-T, REVEL 0.01, CADD 4.37
- A74D (p.Ala74Asp), gnomAD 12-6773711-C-A, REVEL 0.04, CADD 11.30
- A74G (p.Ala74Gly), gnomAD 12-6773711-C-G, REVEL 0.04, CADD 10.80
- A74A (p.Ala74Ala), gnomAD 12-6773712-C-A, CADD 4.28
- A75D (p.Ala75Asp), rs774677549, ClinGen CA6415213, ClinVar RCV004194352, 1000Genomes rs774677549, REVEL 0.01, CADD 3.04, Uncertain significance, not specified
- A75T (p.Ala75Thr), TOPMed rs1419243888, REVEL 0.01, CADD 8.41
- A75V (p.Ala75Val), 1000Genomes rs774677549, ExAC rs774677549, TOPMed rs774677549, gnomAD rs774677549, REVEL 0.01, CADD 3.76, Uncertain significance
- A75P (p.Ala75Pro), gnomAD 12-6773710-GC-G, CADD 21.10
- A75S (p.Ala75Ser), gnomAD 12-6773713-G-T, REVEL 0.01, CADD 6.25
Public LAG3 analysis runs
- LAG3 analysis run — LAG3 (925 variants) — completed 2026-08-21