HLA-A (P04439) variants and mutations
HLA-A (also known as P04439) is a human protein-coding gene encoding a HLA class I histocompatibility antigen, A alpha chain protein. It displays intracellularly derived peptides at the cell surface for surveillance by CD8 T cells and natural-killer-cell receptors. Extreme allelic diversity shapes antiviral and antitumor immunity and can influence susceptibility to autoimmune disease and drug hypersensitivity. This analysis covers 1,288 HLA-A variants and mutations. Of these, 98% have computational variant effect predictions. Disease context includes diffuse large B-cell lymphoma, HIV infectious disease, and COVID-19. Example HLA-A variants include M1?, A2P, and A2T.
Variant analysis overview
- Gene: HLA-A
- Protein: P04439
- UniProt accession: P04439
- Organism: Homo sapiens
- Variants analyzed: 1288
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 1,172 unspecified-consequence records; 32 frameshift variants; 53 missense variants; 21 synonymous variants; 5 in-frame deletions; 1 in-frame insertions; 1 stop-gained variants; 2 splice-region variants; 1 substitution
- Prediction scores: 1,268 variants have prediction scores (98% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: diffuse large B-cell lymphoma, HIV infectious disease, COVID-19, squamous cell lung carcinoma, head and neck squamous cell carcinoma, cervical squamous cell carcinoma, acute myeloid leukemia, nasopharyngeal neoplasm, melanocytic neoplasm, spitz nevus, urinary bladder cancer, Burkitt lymphoma.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 9 binding sites; 9 post-translational modification sites.
- Structural context: 226 variants have structural context.
- PTM context: 17 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 HLA-A variants
Examples include M1?, A2P, A2T, A2V, A2R, A2S, A2G, A2D. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV65144
- A2P (p.Ala2Pro), NCI-TCGA TCGA novel, Ensembl rs1770933332, REVEL 0.25, CADD 18.50, Variant assessed as somatic; moderate impact.
- A2T (p.Ala2Thr), Ensembl rs1770933332, REVEL 0.14, CADD 12.40
- A2V (p.Ala2Val), rs200058378, Ensembl rs200058378, REVEL 0.15, CADD 12.30, Variant assessed as somatic; moderate impact.
- A2R (p.Ala2Arg), gnomAD 6-29942556-GGC-G, CADD 21.90
- A2S (p.Ala2Ser), gnomAD 6-29942557-G-T, REVEL 0.17, CADD 11.40
- A2G (p.Ala2Gly), gnomAD 6-29942558-C-G, REVEL 0.09, CADD 12.80
- A2D (p.Ala2Asp), gnomAD 6-29942558-C-A, REVEL 0.16, CADD 15.70
- A2A (p.Ala2Ala), gnomAD 6-29942559-C-A, CADD 10.70
- V3D (p.Val3Asp), gnomAD rs1408894247, REVEL 0.23, CADD 21.40
- V3F (p.Val3Phe), cosmic curated COSV65144, 1000Genomes rs41541013, ExAC rs41541013, gnomAD rs41541013, REVEL 0.15, CADD 14.90
- V3I (p.Val3Ile), 1000Genomes rs41541013, ExAC rs41541013, gnomAD rs41541013, UniProt VAR 082315, REVEL 0.12, CADD 8.03, Benign, in allele A*34:01
- V3L (p.Val3Leu), 1000Genomes rs41541013, ExAC rs41541013, gnomAD rs41541013, REVEL 0.19, CADD 14.40
- V3S (p.Val3Ser), rs770877280, gnomAD 6-29942557-GC-G, CADD 19.10
- V3G (p.Val3Gly), gnomAD 6-29942559-C-CGG, CADD 20.90
- V3A (p.Val3Ala), gnomAD 6-29942561-T-C, REVEL 0.12, CADD 12.00
- V3V (p.Val3Val), rs751579782, gnomAD 6-29942562-C-T, CADD 9.94
- M4I (p.Met4Ile), gnomAD rs1770936543, REVEL 0.13, CADD 18.90
- M4K (p.Met4Lys), 1000Genomes rs555527051, gnomAD rs555527051, REVEL 0.24, CADD 15.20
- M4R (p.Met4Arg), 1000Genomes rs555527051, gnomAD rs555527051, REVEL 0.23, CADD 17.50
- M4T (p.Met4Thr), 1000Genomes rs555527051, gnomAD rs555527051, REVEL 0.15, CADD 10.70
- M4V (p.Met4Val), cosmic curated COSV65136, 1000Genomes rs79326316, ExAC rs79326316, gnomAD rs79326316, REVEL 0.12, CADD 4.58
- M4W (p.Met4Trp), gnomAD 6-29942561-TC-T, CADD 19.10
- M4L (p.Met4Leu), gnomAD 6-29942563-A-T, REVEL 0.15, CADD 4.15
- A5E (p.Ala5Glu), ExAC rs755858715, gnomAD rs755858715, REVEL 0.19, CADD 4.26
- A5P (p.Ala5Pro), cosmic curated COSV99060, 1000Genomes rs41541913, ESP rs41541913, ExAC rs41541913, REVEL 0.27, CADD 15.90, Benign, in allele A*80:01
- A5S (p.Ala5Ser), 1000Genomes rs41541913, ESP rs41541913, ExAC rs41541913, gnomAD rs41541913, REVEL 0.11, CADD 15.00
- A5T (p.Ala5Thr), 1000Genomes rs41541913, ESP rs41541913, ExAC rs41541913, gnomAD rs41541913, REVEL 0.14, CADD 15.90
- A5V (p.Ala5Val), ExAC rs755858715, gnomAD rs755858715, REVEL 0.21, CADD 8.71
- A5R (p.Ala5Arg), gnomAD 6-29942564-TG-T, CADD 22.80
- A5G (p.Ala5Gly), gnomAD 6-29942566-GC-G, CADD 13.40
- A5A (p.Ala5Ala), rs41548614, gnomAD 6-29942568-G-T, CADD 7.94
- P6H (p.Pro6His), gnomAD rs1292284887, REVEL 0.14, CADD 18.70
- P6L (p.Pro6Leu), gnomAD rs1292284887, REVEL 0.11, CADD 19.40
- P6R (p.Pro6Arg), gnomAD rs1292284887, REVEL 0.18, CADD 18.60
- P6A (p.Pro6Ala), gnomAD 6-29942569-C-G, REVEL 0.13, CADD 18.00
- P6T (p.Pro6Thr), gnomAD 6-29942569-C-A, REVEL 0.15, CADD 18.60
- P6S (p.Pro6Ser), gnomAD 6-29942569-C-T, REVEL 0.12, CADD 16.00
- P6P (p.Pro6Pro), gnomAD 6-29942571-C-A, CADD 7.64
- R7* (p.Arg7Ter), NCI-TCGA Cosmic COSV6513, cosmic curated COSV65138, ExAC rs749604425, CADD 26.00, Variant assessed as somatic; high impact.
- R7G (p.Arg7Gly), rs749604425, NCI-TCGA Cosmic COSV6513, ExAC rs749604425, REVEL 0.24, CADD 10.60, Variant assessed as somatic; moderate impact.
- R7P (p.Arg7Pro), Ensembl rs1562680966, REVEL 0.19, CADD 20.80
- R7Q (p.Arg7Gln), NCI-TCGA Cosmic COSV6514, cosmic curated COSV65145, REVEL 0.13, CADD 21.30, Variant assessed as somatic; moderate impact.
- R7N (p.Arg7Asn), gnomAD 6-29942565-GGC-G, CADD 19.90
- R7E (p.Arg7Glu), gnomAD 6-29942567-CG-C, CADD 17.40
- R7del (p.Arg7del), gnomAD 6-29942571-CCGA-C, CADD 8.04
- R7L (p.Arg7Leu), gnomAD 6-29942572-C-CT, CADD 21.70
- R7R (p.Arg7Arg), rs749604425, gnomAD 6-29942572-C-A, CADD 6.13
- T8I (p.Thr8Ile), gnomAD rs1195498708, REVEL 0.09, CADD 16.70
- T8P (p.Thr8Pro), Ensembl rs2127582097, REVEL 0.16, CADD 22.60
- T8S (p.Thr8Ser), gnomAD 6-29942575-A-T, REVEL 0.17, CADD 21.00
- T8A (p.Thr8Ala), gnomAD 6-29942575-A-G, REVEL 0.18, CADD 17.90
- T8N (p.Thr8Asn), gnomAD 6-29942576-C-A, REVEL 0.11, CADD 19.00
- T8T (p.Thr8Thr), rs1394648027, gnomAD 6-29942577-C-T, CADD 8.95
- L9F (p.Leu9Phe), gnomAD rs1450362906, REVEL 0.10, CADD 16.20
- L9H (p.Leu9His), ExAC rs769009978, REVEL 0.20, CADD 22.80
- L9I (p.Leu9Ile), gnomAD rs1450362906, REVEL 0.09, CADD 19.10
- L9R (p.Leu9Arg), cosmic curated COSV65138, REVEL 0.25, CADD 22.90
- L9V (p.Leu9Val), gnomAD rs1450362906, REVEL 0.12, CADD 15.30
- L9S (p.Leu9Ser), gnomAD 6-29942575-AC-A, CADD 18.30
- L9P (p.Leu9Pro), gnomAD 6-29942578-CT-C, CADD 22.40
- L9L (p.Leu9Leu), gnomAD 6-29942580-C-G, CADD 13.80
- L10F (p.Leu10Phe), 1000Genomes rs1143146, ESP rs1143146, ExAC rs1143146, gnomAD rs1143146, REVEL 0.02, CADD 10.70
- L10I (p.Leu10Ile), 1000Genomes rs1143146, ESP rs1143146, ExAC rs1143146, gnomAD rs1143146, REVEL 0.02, CADD 13.50
- L10V (p.Leu10Val), cosmic curated COSV65136, 1000Genomes rs1143146, ESP rs1143146, ExAC rs1143146, REVEL 0.02, CADD 13.10, Benign, in allele A*02:01, allele A*02:05, allele A*23:01, allele A*24:02, allele A*25:0
- L10P (p.Leu10Pro), gnomAD 6-29942579-TCC-T, CADD 22.20
- L10S (p.Leu10Ser), gnomAD 6-29942579-TC-T, CADD 22.50
- L10R (p.Leu10Arg), gnomAD 6-29942582-T-G, REVEL 0.20, CADD 23.10
- L10H (p.Leu10His), gnomAD 6-29942582-T-A, REVEL 0.14, CADD 23.10
- L10L (p.Leu10Leu), rs201039698, gnomAD 6-29942583-C-T, CADD 11.70
- L11M (p.Leu11Met), cosmic curated COSV10611, ESP rs142768093, ExAC rs142768093, gnomAD rs142768093, REVEL 0.15, CADD 23.00
- L11P (p.Leu11Pro), Ensembl rs2127582135, REVEL 0.22, CADD 23.60
- L11R (p.Leu11Arg), cosmic curated COSV65140, REVEL 0.24, CADD 23.20
- p.Leu11 Leu13del, rs776873046, gnomAD 6-29942577-CCTCCT, CADD 12.20
- L11C (p.Leu11Cys), gnomAD 6-29942582-TC-T, CADD 18.80
- L11V (p.Leu11Val), gnomAD 6-29942584-C-G, REVEL 0.11, CADD 22.60
- L11L (p.Leu11Leu), gnomAD 6-29942584-C-T, CADD 14.80
- L11Q (p.Leu11Gln), gnomAD 6-29942585-T-A, REVEL 0.17, CADD 23.10
- L12P (p.Leu12Pro), cosmic curated COSV65143, REVEL 0.20, CADD 24.10
- L12Y (p.Leu12Tyr), gnomAD 6-29942585-TG-T, CADD 23.10
- L12L (p.Leu12Leu), gnomAD 6-29942587-C-T, CADD 13.70
- L12I (p.Leu12Ile), gnomAD 6-29942587-C-A, REVEL 0.12, CADD 22.40
- L12V (p.Leu12Val), gnomAD 6-29942587-C-G, REVEL 0.11, CADD 20.00
- L12Q (p.Leu12Gln), gnomAD 6-29942588-T-A, REVEL 0.16, CADD 23.90
- L12R (p.Leu12Arg), gnomAD 6-29942588-T-G, REVEL 0.22, CADD 23.90
- L13R (p.Leu13Arg), cosmic curated COSV65141, REVEL 0.25, CADD 24.20
- p.Leu13dup, gnomAD 6-29942576-C-CCCT, CADD 9.05
- L13del (p.Leu13del), gnomAD 6-29942576-CCCT-C, CADD 8.66
- L13S (p.Leu13Ser), gnomAD 6-29942588-TA-T, CADD 21.40
- L13F (p.Leu13Phe), gnomAD 6-29942590-C-T, REVEL 0.14, CADD 21.60
- L13I (p.Leu13Ile), gnomAD 6-29942590-C-A, REVEL 0.15, CADD 21.30
- L13V (p.Leu13Val), gnomAD 6-29942590-C-G, REVEL 0.13, CADD 21.60
- L13H (p.Leu13His), gnomAD 6-29942591-T-A, REVEL 0.19, CADD 24.10
- L13P (p.Leu13Pro), gnomAD 6-29942591-T-C, REVEL 0.24, CADD 24.40
- L13L (p.Leu13Leu), gnomAD 6-29942592-C-A, CADD 9.81
- S14* (p.Ser14Ter), 1000Genomes rs2230954, ESP rs2230954, ExAC rs2230954, gnomAD rs2230954, CADD 28.50
- S14L (p.Ser14Leu), rs2230954, cosmic curated COSV65136, ClinVar RCV002306447, 1000Genomes rs2230954, REVEL 0.05, CADD 5.43, no classification for the single variant, in allele A*29:02, allele A*31:01, allele A*32:01, allele A*33:01 and allele A*7
- S14P (p.Ser14Pro), Ensembl rs2127582142, REVEL 0.13, CADD 22.00
- S14W (p.Ser14Trp), 1000Genomes rs2230954, ESP rs2230954, ExAC rs2230954, gnomAD rs2230954, REVEL 0.15, CADD 17.30
- S14F (p.Ser14Phe), gnomAD 6-29942592-C-CT, CADD 20.20
- S14R (p.Ser14Arg), gnomAD 6-29942592-CT-C, CADD 19.50
- S14T (p.Ser14Thr), gnomAD 6-29942593-T-A, REVEL 0.10, CADD 15.40
- S14A (p.Ser14Ala), gnomAD 6-29942593-T-G, REVEL 0.08, CADD 12.50
- S14S (p.Ser14Ser), gnomAD 6-29942595-G-T, CADD 11.50
- G15R (p.Gly15Arg), ExAC rs766567333, gnomAD rs766567333, REVEL 0.14, CADD 22.80
- G15W (p.Gly15Trp), gnomAD 6-29942595-G-GT, CADD 22.40
- G15V (p.Gly15Val), gnomAD 6-29942597-G-T, REVEL 0.10, CADD 21.80
- G15E (p.Gly15Glu), gnomAD 6-29942597-G-A, REVEL 0.12, CADD 22.00
- G15A (p.Gly15Ala), gnomAD 6-29942597-G-C, REVEL 0.15, CADD 17.30
- G15G (p.Gly15Gly), gnomAD 6-29942598-G-T, CADD 13.00
- A16D (p.Ala16Asp), cosmic curated COSV65141, REVEL 0.23, CADD 21.10
- A16G (p.Ala16Gly), cosmic curated COSV10095, Ensembl rs41554816, REVEL 0.12, CADD 17.60
- A16P (p.Ala16Pro), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10095, NCI-TCGA Cosmic COSV6514, REVEL 0.19, CADD 16.10, Variant assessed as somatic; moderate impact.
- A16S (p.Ala16Ser), ExAC rs762796897, TOPMed rs762796897, gnomAD rs762796897, REVEL 0.11, CADD 8.77
- A16T (p.Ala16Thr), ExAC rs762796897, TOPMed rs762796897, gnomAD rs762796897, REVEL 0.09, CADD 6.85
- A16V (p.Ala16Val), Ensembl rs41554816, REVEL 0.08, CADD 13.20
- A16A (p.Ala16Ala), gnomAD 6-29942601-C-G, CADD 10.30
- L17M (p.Leu17Met), ExAC rs751524208, gnomAD rs751524208, REVEL 0.16, CADD 22.90
- L17P (p.Leu17Pro), cosmic curated COSV10970, Ensembl rs2127582173, REVEL 0.19, CADD 23.80
- L17Q (p.Leu17Gln), Ensembl rs2127582173, REVEL 0.17, CADD 23.60
- L17V (p.Leu17Val), ExAC rs751524208, gnomAD rs751524208, REVEL 0.15, CADD 22.70
- L17W (p.Leu17Trp), gnomAD 6-29942599-GC-G, CADD 20.20
- L17L (p.Leu17Leu), gnomAD 6-29942602-C-T, CADD 15.10
- L17R (p.Leu17Arg), gnomAD 6-29942603-T-G, REVEL 0.24, CADD 23.70
- A18G (p.Ala18Gly), TOPMed rs1279237267, gnomAD rs1279237267, REVEL 0.14, CADD 16.80
- A18S (p.Ala18Ser), gnomAD rs1454564491, REVEL 0.13, CADD 20.90
- A18V (p.Ala18Val), TOPMed rs1279237267, gnomAD rs1279237267, REVEL 0.14, CADD 8.26
- p.Ala18 Leu19del, gnomAD 6-29942597-GGGCCC, CADD 12.20
- A18P (p.Ala18Pro), gnomAD 6-29942603-TG-T, CADD 22.20
- A18T (p.Ala18Thr), gnomAD 6-29942605-G-A, REVEL 0.11, CADD 14.00
- A18D (p.Ala18Asp), gnomAD 6-29942606-C-A, REVEL 0.25, CADD 17.50
- A18A (p.Ala18Ala), gnomAD 6-29942607-C-G, CADD 10.10
- L19* (p.Leu19Ter), gnomAD 6-29942605-GC-G, CADD 15.30
- p.Leu19 Thr20del, gnomAD 6-29942605-GCCCTG, CADD 13.80
- L19R (p.Leu19Arg), gnomAD 6-29942608-CT-C, CADD 22.70
- L19V (p.Leu19Val), gnomAD 6-29942608-C-G, REVEL 0.17, CADD 14.60
- L19L (p.Leu19Leu), gnomAD 6-29942608-C-T, CADD 14.30
- L19M (p.Leu19Met), gnomAD 6-29942608-C-A, REVEL 0.16, CADD 22.70
- L19Q (p.Leu19Gln), gnomAD 6-29942609-T-A, REVEL 0.22, CADD 22.90
- L19P (p.Leu19Pro), gnomAD 6-29942609-T-C, REVEL 0.23, CADD 23.00
- T20A (p.Thr20Ala), Ensembl rs2127582183, REVEL 0.17, CADD 23.20
- T20I (p.Thr20Ile), ExAC rs766935810, gnomAD rs766935810, REVEL 0.16, CADD 22.90
- T20N (p.Thr20Asn), ExAC rs766935810, gnomAD rs766935810, REVEL 0.13, CADD 22.60
- T20P (p.Thr20Pro), gnomAD 6-29942610-GA-G, CADD 23.60
- T20S (p.Thr20Ser), gnomAD 6-29942611-A-T, REVEL 0.14, CADD 23.10
- T20T (p.Thr20Thr), rs1224972157, gnomAD 6-29942613-C-T, CADD 12.30
- Q21E (p.Gln21Glu), gnomAD rs1249775058, REVEL 0.15, CADD 8.48
- Q21K (p.Gln21Lys), gnomAD rs1249775058, REVEL 0.24, CADD 8.32
- Q21R (p.Gln21Arg), gnomAD 6-29942611-AC-A, CADD 23.20
- Q21* (p.Gln21Ter), gnomAD 6-29942614-C-T, CADD 32.00
- Q21P (p.Gln21Pro), gnomAD 6-29942615-A-C, REVEL 0.15, CADD 14.40
- Q21L (p.Gln21Leu), gnomAD 6-29942615-A-T, REVEL 0.07, CADD 18.10
- Q21H (p.Gln21His), gnomAD 6-29942616-G-T, REVEL 0.12, CADD 22.80
- Q21Q (p.Gln21Gln), gnomAD 6-29942616-G-A, CADD 13.90
- T22A (p.Thr22Ala), gnomAD rs1341761581, REVEL 0.18, CADD 23.00
- T22I (p.Thr22Ile), cosmic curated COSV10468, ExAC rs750005260, gnomAD rs750005260, REVEL 0.22, CADD 22.60
- T22N (p.Thr22Asn), ExAC rs750005260, gnomAD rs750005260, REVEL 0.17, CADD 22.10
- T22P (p.Thr22Pro), gnomAD rs1341761581, REVEL 0.18, CADD 23.30
- T22S (p.Thr22Ser), gnomAD 6-29942617-A-T, REVEL 0.16, CADD 20.90
- T22T (p.Thr22Thr), gnomAD 6-29942619-C-G, CADD 12.90
- W23* (p.Trp23Ter), NCI-TCGA Cosmic COSV6514, cosmic curated COSV65145, CADD 35.00, Variant assessed as somatic; high impact., in allele A*74:01
- W23R (p.Trp23Arg), 1000Genomes rs41564012, ESP rs41564012, ExAC rs41564012, gnomAD rs41564012, REVEL 0.09, CADD 10.50, Benign, in allele A*74:01
- W23S (p.Trp23Ser), Ensembl rs2127582208, REVEL 0.09, CADD 23.70
- W23G (p.Trp23Gly), gnomAD 6-29942617-AC-A, CADD 22.70
- W23C (p.Trp23Cys), gnomAD 6-29942620-TGG-T, CADD 23.00
- W23L (p.Trp23Leu), gnomAD 6-29942621-G-T, REVEL 0.06, CADD 22.50
- A24E (p.Ala24Glu), gnomAD rs1206196955, REVEL 0.17, CADD 22.90
- A24G (p.Ala24Gly), gnomAD rs1206196955, REVEL 0.16, CADD 24.20
- A24S (p.Ala24Ser), Ensembl rs1770948309, REVEL 0.15, CADD 23.50
- A24T (p.Ala24Thr), cosmic curated COSV65139, REVEL 0.20, CADD 23.90
- A24V (p.Ala24Val), gnomAD rs1206196955, REVEL 0.18, CADD 25.00
- A24R (p.Ala24Arg), gnomAD 6-29942620-TG-T, CADD 23.10
- A24P (p.Ala24Pro), gnomAD 6-29942623-G-C, REVEL 0.17, CADD 23.90
- A24A (p.Ala24Ala), rs1136656, gnomAD 6-29942625-G-C, CADD 8.64
- G25A (p.Gly25Ala), Ensembl rs199474346, REVEL 0.24, CADD 28.10
- G25R (p.Gly25Arg), ExAC rs200993279, gnomAD rs200993279, REVEL 0.13, CADD 30.00
- G25C (p.Gly25Cys), gnomAD 6-29942626-G-T, REVEL 0.23, CADD 33.00
- G25S (p.Gly25Ser), gnomAD 6-29942626-G-A, REVEL 0.25, CADD 33.00
- G25D (p.Gly25Asp), gnomAD 6-29942757-G-A, REVEL 0.14, CADD 25.80
- G25V (p.Gly25Val), gnomAD 6-29942757-G-T, REVEL 0.20, CADD 31.00
Public HLA-A analysis runs
- HLA-A analysis run — HLA-A (1,288 variants) — completed 2026-08-19