HBB (Hemoglobin subunit beta) variants and mutations
The associated protein is Hemoglobin subunit beta. Beta-globin, one of the two major protein chains in adult hemoglobin. Hemoglobin uses these chains to transport oxygen from the lungs to tissues, and HBB variants are associated with sickle-cell disease and beta-thalassemia. This CATVariant analysis covers 775 HBB variants and mutations. Disease context includes sickle cell disease; this analysis is associated with sickle cell disease. Available evidence includes missense variants, protein structure.
Variant analysis overview
- Gene: HBB
- Protein: Hemoglobin subunit beta
- UniProt accession: P68871
- Organism: Homo sapiens
- Variants analyzed: 775
- Variant scope: all variants
- Completed: 2026-05-15
Variant and mutation evidence
- Variant composition: 636 unspecified-consequence records; 2 stop retained variant; 95 synonymous variants; 16 frameshift variants; 1 stop lost; 20 missense variants; 3 splice-region variants; 1 stop-gained variants; 1 in-frame deletions
- Prediction scores: 753 variants have prediction scores (97% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: sickle cell disease, Beta-thalassemia, dominant beta-thalassemia, beta thalassemia, hemoglobin M disease, Hereditary persistence of fetal hemoglobin - beta-thalassemia, beta-thalassemia HBB/LCRB, Autosomal dominant methemoglobinemia, erythrocytosis, familial, 6, anemia, Heinz body anemia, hemolytic anemia.
Protein structure and variant hotspots
- Protein features: 1 domains; 6 binding sites; 17 post-translational modification sites.
- Structural context: 759 variants have structural context.
- PTM context: 80 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, ClinGen, PharmGKB, MaveDB, LitVar.
Notable HBB variants
Examples include M1I, M1K, M1L, M1R, M1T, M1V, V2A, V2E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs33930702, ClinGen CA125383, ClinVar RCV000016783, ClinVar RCV000506641, ESM-1b 1.00, AlphaMissense 0.67, Likely pathogenic, beta Thalassemia; not provided
- M1K (p.Met1Lys), rs33941849, ClinGen CA217115650, ClinVar RCV000588257, ClinVar RCV000985744, ESM-1b 1.00, AlphaMissense 0.73, Pathogenic/Likely pathogenic, not provided; beta Thalassemia
- M1L (p.Met1Leu), rs34563000, ClinGen CA379275050, ClinVar RCV001078260, ClinVar RCV001811644, ESM-1b 0.23, AlphaMissense 0.24, Pathogenic/Likely pathogenic, not provided; beta Thalassemia
- M1R (p.Met1Arg), rs33941849, ClinGen CA125299, ClinVar RCV000016691, ClinVar RCV000505904, ESM-1b 1.00, AlphaMissense 0.74, Pathogenic, Erythrocytosis, familial, 6; Heinz body anemia; Beta-thalassemia HBB/LCRB
- M1T (p.Met1Thr), rs33941849, ClinGen CA125301, ClinVar RCV000016692, ClinVar RCV000016693, ESM-1b 1.00, AlphaMissense 0.54, Pathogenic, Beta-thalassemia HBB/LCRB; METHEMOGLOBINEMIA, BETA TYPE; Heinz body anemia
- M1V (p.Met1Val), rs34563000, ClinGen CA217115654, ClinVar RCV000507448, ClinVar RCV000780324, ESM-1b 0.34, AlphaMissense 0.16, Pathogenic, Hemoglobinopathy; not provided; Dominant beta-thalassemia
- V2A (p.Val2Ala), rs33949930, ClinGen CA125122, ClinVar RCV000016563, ClinVar RCV000781459, REVEL 0.79, ESM-1b 1.00, Conflicting interpretations, not specified; not provided
- V2E (p.Val2Glu), rs33949930, ClinGen CA124834, ClinVar RCV000016327, TOPMed rs33949930, ESM-1b 1.00, AlphaMissense 0.81, other, HEMOGLOBIN DOHA
- V2G (p.Val2Gly), rs33949930, ClinGen CA125494, ClinVar RCV000016854, TOPMed rs33949930, REVEL 0.64, ESM-1b 1.00, other, HEMOGLOBIN WATFORD
- V2L (p.Val2Leu), rs33958358, ClinGen CA125444, ClinVar RCV000016824, ClinVar RCV005049378, REVEL 0.72, ESM-1b 1.00, Uncertain significance, Erythrocytosis, familial, 6; Heinz body anemia; Beta-thalassemia HBB/LCRB
- V2M (p.Val2Met), rs33958358, ClinGen CA125180, ClinVar RCV000016609, ClinVar RCV000508674, REVEL 0.82, ESM-1b 1.00, Conflicting interpretations, not specified; not provided
- V2V (p.Val2Val), rs1349384278, gnomAD 11-5227016-C-T, CADD 7.40
- V2C (p.Val2Cys), rs63750475, gnomAD 11-5227017-AC-A, CADD 24.80
- H3L (p.His3Leu), rs33983205, ClinGen CA125381, ClinVar RCV000016782, UniProt VAR 002857, ESM-1b 0.00, AlphaMissense 0.20, other, HEMOGLOBIN GRAZ
- H3P (p.His3Pro), Ensembl rs63750407, MetaLR 0.77, MetaSVM 0.65, Uncertain significance, not specified
- H3Q (p.His3Gln), rs713040, ClinGen CA125078, ClinVar RCV000016529, ClinVar RCV003736540, REVEL 0.48, ESM-1b 0.40, Likely benign, not specified
- H3R (p.His3Arg), rs33983205, ClinGen CA124828, ClinVar RCV000016324, ClinVar RCV001811150, REVEL 0.55, ESM-1b 1.00, Conflicting interpretations, not provided
- H3Y (p.His3Tyr), rs35906307, ClinGen CA124845, ClinVar RCV000016339, UniProt VAR 002860, REVEL 0.59, ESM-1b 1.00, other, HEMOGLOBIN FUKUOKA
- H3H (p.His3His), rs713040, gnomAD 11-5227013-A-G, CADD 0.58
- H3N (p.His3Asn), gnomAD 11-5227015-G-T, REVEL 0.38, ESM-1b 1.00
- L4M (p.Leu4Met), rs34126315, ClinGen CA217115588, ClinVar RCV000780309, ClinVar RCV001272130, REVEL 0.56, ESM-1b 1.00, Uncertain significance, not specified
- L4P (p.Leu4Pro), Ensembl rs63750720, REVEL 0.65, ESM-1b 1.00, Uncertain significance
- L4Q (p.Leu4Gln), rs63750720, ClinGen CA217115574, ClinVar RCV000508469, Ensembl rs63750720, ESM-1b 1.00, AlphaMissense 0.91, Uncertain significance, not specified
- L4V (p.Leu4Val), rs34126315, ClinGen CA217115584, ClinVar RCV001801051, ExAC rs34126315, ESM-1b 1.00, AlphaMissense 0.35, Conflicting interpretations, not provided
- L4L (p.Leu4Leu), rs34126315, gnomAD 11-5227012-G-A, CADD 6.21
- T5A (p.Thr5Ala), cosmic curated COSV10524, ESM-1b 0.48, AlphaMissense 0.23
- T5N (p.Thr5Asn), Ensembl rs63750605, REVEL 0.48, ESM-1b 1.00, Uncertain significance, not specified
- T5P (p.Thr5Pro), Ensembl rs281864509, ESM-1b 1.00, AlphaMissense 0.50
- T5S (p.Thr5Ser), gnomAD 11-5227007-AGT-A, CADD 16.50
- T5T (p.Thr5Thr), gnomAD 11-5227007-A-T, CADD 4.79
- T5I (p.Thr5Ile), gnomAD 11-5227008-G-A, REVEL 0.49, ESM-1b 1.00
- P6A (p.Pro6Ala), rs33912272, ClinGen CA217115556, ClinVar RCV001812585, 1000Genomes rs33912272, REVEL 0.46, ESM-1b 0.00, Likely benign, not provided
- P6H (p.Pro6His), NCI-TCGA Cosmic COSV1000, cosmic curated COSV10009, NCI-TCGA Cosmic COSV5894, TOPMed rs34769005, REVEL 0.52, ESM-1b 0.99, Variant assessed as somatic; moderate impact., in Warwickshire
- P6L (p.Pro6Leu), cosmic curated COSV58943, TOPMed rs34769005, ESM-1b 0.57, AlphaMissense 0.15
- P6R (p.Pro6Arg), rs34769005, ClinGen CA125231, ClinVar RCV000016640, UniProt VAR 002861, ESM-1b 1.00, AlphaMissense 0.19, other, HEMOGLOBIN WARWICKSHIRE
- P6S (p.Pro6Ser), rs33912272, ClinGen CA125420, cosmic curated COSV10646, ClinVar RCV000016806, REVEL 0.44, ESM-1b 0.00, Uncertain significance, not specified; not provided
- P6P (p.Pro6Pro), rs2133589583, gnomAD 11-5227004-A-G, CADD 6.70
- E7* (p.Glu7Ter), rs33930165, ClinGen CA379274985, ClinVar RCV001078259, 1000Genomes rs33930165, CADD 36.00, Pathogenic, in SKCA
- E7A (p.Glu7Ala), rs334, ClinGen CA124861, ClinVar RCV000016352, ClinVar RCV003234907, REVEL 0.50, ESM-1b 0.00, Likely benign, not specified
- E7D (p.Glu7Asp), Ensembl rs1589893600, ESM-1b 0.00, AlphaMissense 0.11, Likely benign, in SKCA
- E7G (p.Glu7Gly), 1000Genomes rs334, ESP rs334, ExAC rs334, gnomAD rs334, ESM-1b 1.00, AlphaMissense 0.13, Pathogenic, in SKCA
- E7K (p.Glu7Lys), rs33930165, ClinGen CA124780, ClinVar RCV000016251, ClinVar RCV000016284, REVEL 0.45, ESM-1b 1.00, other, Dominant beta-thalassemia; Beta-thalassemia HBB/LCRB; Hb SS disease
- E7M (p.Glu7Met), rs193922552, ClinGen CA342851, ClinVar RCV000029966, Ensembl rs193922552, ESM-1b 1.00, AlphaMissense 0.53, Likely pathogenic, beta Thalassemia
- E7Q (p.Glu7Gln), rs33930165, ClinGen CA124989, ClinVar RCV000016448, ClinVar RCV005055515, ESM-1b 0.00, AlphaMissense 0.14, Uncertain significance, not specified
- E7V (p.Glu7Val), rs334, ClinGen CA125138, ClinVar RCV000016286, ClinVar RCV000016573, REVEL 0.54, ESM-1b 1.00, other, Dominant beta-thalassemia; Beta-thalassemia HBB/LCRB; Hb SS disease
- E8* (p.Glu8Ter), rs34948328, ClinGen CA379274972, ClinVar RCV001078316, ClinVar RCV003478695, CADD 37.00, Pathogenic, in G-Siriraj
- E8D (p.Glu8Asp), rs138405215, NCI-TCGA Cosmic COSV5894, cosmic curated COSV58942, ESP rs138405215, ESM-1b 0.00, AlphaMissense 0.59, Uncertain significance, not provided
- E8G (p.Glu8Gly), rs34387455, ClinGen CA124863, ClinVar RCV000016353, ClinVar RCV000756237, REVEL 0.83, ESM-1b 1.00, Likely benign, not specified; not provided
- E8K (p.Glu8Lys), rs34948328, ClinGen CA125168, cosmic curated COSV10524, ClinVar RCV000016602, ESM-1b 1.00, AlphaMissense 0.95, Uncertain significance, not specified; not provided
- E8Q (p.Glu8Gln), TOPMed rs34948328, REVEL 0.66, ESM-1b 0.00, Pathogenic, in G-Siriraj
- E8del (p.Glu8del), rs63750928, gnomAD 11-5226997-TCTC-T, CADD 15.40
- K9* (p.Lys9Ter), cosmic curated COSV58943
- K9E (p.Lys9Glu), rs33926764, ClinGen CA125050, ClinVar RCV000016511, ClinVar RCV001269803, ESM-1b 1.00, AlphaMissense 0.63, Pathogenic, not provided
- K9M (p.Lys9Met), rs33932981, ClinGen CA125428, ClinVar RCV000016814, Ensembl rs33932981, ESM-1b 1.00, AlphaMissense 0.55, other, HEMOGLOBIN NAKANO
- K9N (p.Lys9Asn), rs35198910, ClinGen CA125503, cosmic curated COSV58942, ClinVar RCV000016860, ESM-1b 1.00, AlphaMissense 0.86, other, HEMOGLOBIN LIMASSOL
- K9Q (p.Lys9Gln), rs33926764, ClinGen CA124959, ClinVar RCV000016422, UniProt VAR 002869, ESM-1b 1.00, AlphaMissense 0.30, other, HEMOGLOBIN J (LUHE)
- K9R (p.Lys9Arg), rs33932981, ClinGen CA125468, ClinVar RCV000016839, Ensembl rs33932981, ESM-1b 0.00, AlphaMissense 0.12, other, HEMOGLOBIN LUCKNOW
- K9T (p.Lys9Thr), rs33932981, ClinGen CA130022, ClinVar RCV000030668, UniProt VAR 002870, ESM-1b 1.00, AlphaMissense 0.40, other, HEMOGLOBIN RIO GRANDE
- K9V (p.Lys9Val), rs35497102, gnomAD 11-5226995-CTT-C, CADD 24.70
- K9K (p.Lys9Lys), rs35198910, gnomAD 11-5226995-C-T, CADD 4.53
- S10A (p.Ser10Ala), Ensembl rs1589893571, ESM-1b 0.00, AlphaMissense 0.06
- S10C (p.Ser10Cys), rs33918131, ClinGen CA125110, ClinVar RCV000016556, ClinVar RCV000508345, REVEL 0.53, ESM-1b 1.00, Benign/Likely benign, not specified; not provided
- S10Y (p.Ser10Tyr), rs33918131, ClinGen CA125538, ClinVar RCV000016858, ClinVar RCV000016886, ESM-1b 1.00, AlphaMissense 0.32, other, HEMOGLOBIN D (AGRI)
- S10S (p.Ser10Ser), rs1847587096, gnomAD 11-5226992-A-C, CADD 0.62
- S10V (p.Ser10Val), rs35699606, gnomAD 11-5226994-A-AC, CADD 22.80
- S10T (p.Ser10Thr), gnomAD 11-5226994-A-T, REVEL 0.57, ESM-1b 0.00
- A11D (p.Ala11Asp), rs33947457, ClinGen CA124726, cosmic curated COSV10812, ClinVar RCV000016250, ESM-1b 1.00, AlphaMissense 0.36, other, HEMOGLOBIN ANKARA
- A11T (p.Ala11Thr), rs63750717, ClinGen CA217115444, ClinVar RCV000507628, TOPMed rs63750717, REVEL 0.53, ESM-1b 0.00, Conflicting interpretations, not specified
- A11V (p.Ala11Val), rs33947457, ClinGen CA125466, cosmic curated COSV10009, ClinVar RCV000016838, REVEL 0.57, ESM-1b 0.00, other, HEMOGLOBIN IRAQ-HALABJA
- A11A (p.Ala11Ala), rs35799536, gnomAD 11-5226989-G-T, CADD 0.09
- V12D (p.Val12Asp), rs35140348, ClinGen CA125235, ClinVar RCV000016642, UniProt VAR 002873, ESM-1b 1.00, AlphaMissense 0.99, other, HEMOGLOBIN WINDSOR
- V12F (p.Val12Phe), rs33974228, ClinGen CA125412, ClinVar RCV000016800, ClinVar RCV000759071, ESM-1b 1.00, AlphaMissense 0.78, Uncertain significance, not provided
- V12I (p.Val12Ile), rs33974228, ClinGen CA124888, ClinVar RCV000016370, ClinVar RCV000016863, REVEL 0.52, ESM-1b 0.51, other, HEMOGLOBIN O (TIBESTI)
- V12V (p.Val12Val), gnomAD 11-5226986-A-G, CADD 1.07
- T13N (p.Thr13Asn), Ensembl rs1589893524, ESM-1b 0.00, AlphaMissense 0.11
- T13S (p.Thr13Ser), Ensembl rs1589893527, REVEL 0.59, ESM-1b 0.00
- T13I (p.Thr13Ile), gnomAD 11-5226984-G-A, REVEL 0.55, ESM-1b 0.29
- T13L (p.Thr13Leu), rs34856846, gnomAD 11-5226985-TA-T, CADD 13.00
- A14D (p.Ala14Asp), rs35203747, ClinGen CA124955, cosmic curated COSV58942, ClinVar RCV000016420, ESM-1b 0.00, AlphaMissense 0.19, other, HEMOGLOBIN J (LENS)
- A14G (p.Ala14Gly), TOPMed rs35203747, gnomAD rs35203747, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, in J-Lens
- A14S (p.Ala14Ser), rs766266418, NCI-TCGA Cosmic COSV5894, cosmic curated COSV58942, ExAC rs766266418, REVEL 0.56, ESM-1b 0.00, Benign, in J-Lens
- A14T (p.Ala14Thr), rs766266418, ClinGen CA379274909, ClinVar RCV001289993, ExAC rs766266418, ESM-1b 0.00, AlphaMissense 0.07, Uncertain significance, not specified
- A14V (p.Ala14Val), rs35203747, ClinGen CA379274902, ClinVar RCV000759799, ClinVar RCV001194401, REVEL 0.59, ESM-1b 0.32, Uncertain significance, not specified; not provided
- A14L (p.Ala14Leu), gnomAD 11-5226983-A-AAG, CADD 1.29
- L15P (p.Leu15Pro), rs33935445, ClinGen CA125145, ClinVar RCV000016584, ClinVar RCV000508682, REVEL 0.82, ESM-1b 1.00, Uncertain significance, Erythrocytosis, familial, 6; Heinz body anemia; Beta-thalassemia HBB/LCRB
- L15R (p.Leu15Arg), rs33935445, ClinGen CA125172, ClinVar RCV000016604, ClinVar RCV000588440, REVEL 0.80, ESM-1b 1.00, Uncertain significance, not provided; not specified
- L15V (p.Leu15Val), TOPMed rs1847585936, ESM-1b 0.22, AlphaMissense 0.10, Uncertain significance, not specified
- L15L (p.Leu15Leu), gnomAD 11-5226977-C-G, CADD 1.27
- W16* (p.Trp16Ter), rs34716011, ClinGen CA217115390, ClinVar RCV000508624, ClinVar RCV000589075, CADD 36.00, Pathogenic, in Belfast
- W16G (p.Trp16Gly), rs33946157, ClinGen CA125124, ClinVar RCV000016564, UniProt VAR 002878, ESM-1b 1.00, AlphaMissense 0.90, other, HEMOGLOBIN RANDWICK
- W16R (p.Trp16Arg), rs33946157, ClinGen CA124742, ClinVar RCV000016261, UniProt VAR 002879, ESM-1b 1.00, AlphaMissense 0.99, other, HEMOGLOBIN BELFAST
- W16V (p.Trp16Val), rs35383398, gnomAD 11-5226976-A-AC, CADD 23.80
- G17A (p.Gly17Ala), NCI-TCGA Cosmic COSV1000, Variant assessed as somatic; high impact., in D-Bushman
- G17C (p.Gly17Cys), TOPMed rs63751285, gnomAD rs63751285, ESM-1b 1.00, AlphaMissense 0.28
- G17D (p.Gly17Asp), rs33962676, ClinGen CA124935, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10009, REVEL 0.57, ESM-1b 0.74, Conflicting interpretations, not specified; not provided
- G17R (p.Gly17Arg), rs63751285, ClinGen CA124816, ClinVar RCV000016311, UniProt VAR 002881, ESM-1b 1.00, AlphaMissense 0.36, other, HEMOGLOBIN D (BUSHMAN)
- G17S (p.Gly17Ser), cosmic curated COSV10741, TOPMed rs63751285, gnomAD rs63751285, REVEL 0.53, ESM-1b 0.00
- K18E (p.Lys18Glu), rs33986703, ClinGen CA217115373, ClinVar RCV000016512, UniProt VAR 002882, ESM-1b 1.00, AlphaMissense 0.39, other, HEMOGLOBIN NAGASAKI
- K18N (p.Lys18Asn), rs36006214, ClinGen CA124929, ClinVar RCV000016397, UniProt VAR 002883, REVEL 0.65, ESM-1b 1.00, other, HEMOGLOBIN J (AMIENS)
- K18* (p.Lys18Ter), rs33986703, ClinGen CA125257, ClinVar RCV000016655, ClinVar RCV000020337, CADD 42.00, Pathogenic, in Nikosia
- K18Q (p.Lys18Gln), rs33986703, ClinGen CA217115378, ClinVar RCV000016762, UniProt VAR 002884, ESM-1b 1.00, AlphaMissense 0.18, other, HEMOGLOBIN NIKOSIA
- K18R (p.Lys18Arg), gnomAD rs369865419, ESM-1b 1.00, AlphaMissense 0.11
- K18T (p.Lys18Thr), rs369865419, NCI-TCGA Cosmic COSV1000, cosmic curated COSV10009, gnomAD rs369865419, REVEL 0.84, ESM-1b 1.00, Variant assessed as somatic; moderate impact., in Nikosia
- K18K (p.Lys18Lys), rs36006214, gnomAD 11-5226968-C-T, CADD 6.84
- V19G (p.Val19Gly), rs35382661, ClinGen CA217115344, ClinVar RCV000589269, ClinVar RCV001251065, REVEL 0.97, ESM-1b 1.00, Uncertain significance, not provided; not specified
- V19L (p.Val19Leu), Ensembl rs35802118, ESM-1b 0.00, AlphaMissense 0.43
- V19M (p.Val19Met), rs35802118, ClinGen CA125379, ClinVar RCV000016781, UniProt VAR 002885, ESM-1b 1.00, AlphaMissense 0.47, other, HEMOGLOBIN BADEN
- N20D (p.Asn20Asp), rs34866629, ClinGen CA124718, ClinVar RCV000016246, ClinVar RCV005614370, ESM-1b 0.00, AlphaMissense 0.10, Uncertain significance; other, beta Thalassemia; HEMOGLOBIN ALAMO
- N20K (p.Asn20Lys), rs63750840, ClinGen CA124826, ClinVar RCV000016321, ClinVar RCV001811149, REVEL 0.47, ESM-1b 0.00, Conflicting interpretations, not provided; not specified
- N20S (p.Asn20Ser), rs33972047, ClinGen CA125015, ClinVar RCV000016479, ClinVar RCV000016480, ESM-1b 0.00, AlphaMissense 0.08, Pathogenic, not provided; beta Thalassemia
- N20N (p.Asn20Asn), rs63750840, gnomAD 11-5226962-G-A, CADD 0.26
- V21A (p.Val21Ala), Ensembl rs33918474, ESM-1b 0.90, AlphaMissense 0.14
- V21E (p.Val21Glu), rs33918474, ClinGen CA125418, ClinVar RCV000016805, Ensembl rs33918474, ESM-1b 1.00, AlphaMissense 0.45, Uncertain significance, not specified
- V21G (p.Val21Gly), Ensembl rs33918474, REVEL 0.55, ESM-1b 1.00
- V21L (p.Val21Leu), TOPMed rs35890959, gnomAD rs35890959, REVEL 0.56, ESM-1b 1.00, Uncertain significance, not specified
- V21M (p.Val21Met), rs35890959, ClinGen CA125086, cosmic curated COSV58942, ClinVar RCV000016533, REVEL 0.57, ESM-1b 1.00, Pathogenic/Likely pathogenic, Erythrocytosis, familial, 6; Heinz body anemia; Beta-thalassemia HBB/LCRB
- D22E (p.Asp22Glu), gnomAD rs373362317, REVEL 0.55, ESM-1b 0.00
- D22G (p.Asp22Gly), rs33977536, ClinGen CA124805, ClinVar RCV000016305, UniProt VAR 002890, ESM-1b 0.00, AlphaMissense 0.11, other, HEMOGLOBIN CONNECTICUT
- D22H (p.Asp22His), rs33950093, ClinGen CA125385, ClinVar RCV000016784, UniProt VAR 002892, REVEL 0.56, ESM-1b 1.00, other, HEMOGLOBIN KARLSKOGA
- D22N (p.Asp22Asn), rs33950093, ClinGen CA124801, ClinVar RCV000016303, ClinVar RCV004998082, ESM-1b 0.00, AlphaMissense 0.11, Uncertain significance, not provided
- D22V (p.Asp22Val), rs33977536, ClinGen CA217115275, ClinVar RCV001801095, TOPMed rs33977536, ESM-1b 0.72, AlphaMissense 0.25, Uncertain significance, not provided
- D22Y (p.Asp22Tyr), rs33950093, cosmic curated COSV10884, ClinGen CA125253, ClinVar RCV000016653, ESM-1b 1.00, AlphaMissense 0.52, Likely benign, not provided
- D22D (p.Asp22Asp), rs373362317, gnomAD 11-5226956-A-G, CADD 0.20
- E23* (p.Glu23Ter), rs33959855, ClinGen CA217115260, cosmic curated COSV58943, ClinVar RCV001078431, CADD 36.00, Pathogenic, in D-Granada
- E23A (p.Glu23Ala), rs33936254, ClinGen CA124853, ClinVar RCV000016343, ClinVar RCV000016344, REVEL 0.57, ESM-1b 1.00, Conflicting interpretations, not specified; not provided; beta Thalassemia
- E23D (p.Glu23Asp), cosmic curated COSV58943, Ensembl rs281864513, cosmic curated COSV58942, REVEL 0.57, ESM-1b 0.39
- E23G (p.Glu23Gly), rs33936254, ClinGen CA124867, ClinVar RCV000016356, ClinVar RCV000756231, REVEL 0.59, ESM-1b 1.00, Conflicting interpretations, not provided
- E23K (p.Glu23Lys), rs33959855, ClinGen CA124839, cosmic curated COSV10884, NCI-TCGA Cosmic COSV5894, REVEL 0.54, ESM-1b 1.00, Conflicting interpretations, not provided
- E23Q (p.Glu23Gln), rs33959855, ClinGen CA124822, ClinVar RCV000016314, ClinVar RCV000589411, REVEL 0.54, ESM-1b 0.51, Conflicting interpretations, not specified; not provided
- E23V (p.Glu23Val), rs33936254, ClinGen CA124818, ClinVar RCV000016312, ClinVar RCV000759803, ESM-1b 1.00, AlphaMissense 0.08, Uncertain significance, Erythrocytosis, familial, 6; Heinz body anemia; Beta-thalassemia HBB/LCRB
- V24A (p.Val24Ala), rs33945546, ClinGen CA125536, ClinVar RCV000016885, Ensembl rs33945546, ESM-1b 1.00, AlphaMissense 0.19, other, HEMOGLOBIN ZOETERWOUDE
- V24D (p.Val24Asp), rs33945546, ClinGen CA125178, ClinVar RCV000016608, ClinVar RCV000985755, ESM-1b 1.00, AlphaMissense 0.85, Uncertain significance, not provided
- V24F (p.Val24Phe), rs33929459, ClinGen CA125092, cosmic curated COSV58941, ClinVar RCV000016544, REVEL 0.62, ESM-1b 1.00, Pathogenic, Unstable hemoglobin disease
- V24G (p.Val24Gly), rs33945546, ClinGen CA125034, ClinVar RCV000016496, UniProt VAR 002901, ESM-1b 1.00, AlphaMissense 0.48, other, HEMOGLOBIN MIYASHIRO
- V24I (p.Val24Ile), rs33929459, ClinGen CA037454, ClinVar RCV000016576, ClinVar RCV000736024, ESM-1b 1.00, AlphaMissense 0.09, Uncertain significance, not provided
- V24L (p.Val24Leu), rs33929459, ClinGen CA379274808, ClinVar RCV000587770, ExAC rs33929459, ESM-1b 1.00, AlphaMissense 0.31, Uncertain significance, not provided
- G25D (p.Gly25Asp), rs33968721, ClinGen CA125042, ClinVar RCV000016501, UniProt VAR 002902, ESM-1b 1.00, AlphaMissense 0.99, other, HEMOGLOBIN MOSCVA
- G25R (p.Gly25Arg), rs33972975, ClinGen CA125128, ClinVar RCV000016567, UniProt VAR 002903, ESM-1b 1.00, AlphaMissense 0.99, other, HEMOGLOBIN RIVERDALE-BRONX
- G25S (p.Gly25Ser), NCI-TCGA Cosmic COSV5894, cosmic curated COSV58943, ESM-1b 1.00, AlphaMissense 0.95, Uncertain significance, not specified
- G25V (p.Gly25Val), rs33968721, ClinGen CA125151, ClinVar RCV000016587, UniProt VAR 002904, ESM-1b 1.00, AlphaMissense 0.97, other, HEMOGLOBIN SAVANNAH
- G25G (p.Gly25Gly), rs33951465, gnomAD 11-5226947-A-T, CADD 14.90
- G26D (p.Gly26Asp), rs35474880, ClinGen CA124933, ClinVar RCV000016399, UniProt VAR 002905, REVEL 0.69, ESM-1b 1.00, other, HEMOGLOBIN J (AUCKLAND)
- G26R (p.Gly26Arg), rs34404985, ClinGen CA124869, cosmic curated COSV10942, ClinVar RCV000016357, REVEL 0.61, ESM-1b 0.00, other, HEMOGLOBIN G (TAIWAN-AMI)
- G26S (p.Gly26Ser), ExAC rs34404985, gnomAD rs34404985, ESM-1b 0.00, AlphaMissense 0.19
- G26G (p.Gly26Gly), rs373379910, gnomAD 11-5226944-A-C, CADD 17.90
- E27* (p.Glu27Ter), rs33950507, ClinGen CA217115188, ClinVar RCV000507549, ClinVar RCV000674991, CADD 32.00, Pathogenic, in Henri Mondor
- E27A (p.Glu27Ala), rs33915112, ClinGen CA125532, ClinVar RCV000016881, Ensembl rs33915112, ESM-1b 1.00, AlphaMissense 0.47, other, HEMOGLOBIN TRIPOLI
- E27D (p.Glu27Asp), rs281864581, Ensembl rs281864581, ClinGen CA217115164, ClinVar RCV000736023, ESM-1b 0.64, AlphaMissense 0.44, Pathogenic, Hemoglobinopathy
- E27G (p.Glu27Gly), rs33915112, ClinGen CA125438, ClinVar RCV000016820, Ensembl rs33915112, ESM-1b 1.00, AlphaMissense 0.67, Pathogenic, in Henri Mondor
- E27K (p.Glu27Lys), rs33950507, ClinGen CA124838, ClinVar RCV000016329, ClinVar RCV000016330, REVEL 0.72, ESM-1b 1.00, Pathogenic, Dominant beta-thalassemia; Beta-thalassemia HBB/LCRB; Hb SS disease
- E27Q (p.Glu27Gln), 1000Genomes rs33950507, ExAC rs33950507, TOPMed rs33950507, gnomAD rs33950507, ESM-1b 1.00, AlphaMissense 0.31, Pathogenic, in Henri Mondor
- E27V (p.Glu27Val), rs33915112, ClinGen CA124898, ClinVar RCV000016377, UniProt VAR 002908, ESM-1b 1.00, AlphaMissense 0.67, other, HEMOGLOBIN HENRI MONDOR
- A28D (p.Ala28Asp), rs33954632, ClinGen CA125229, cosmic curated COSV10965, ClinVar RCV000016638, REVEL 0.93, ESM-1b 1.00, Pathogenic, not provided
- A28G (p.Ala28Gly), ExAC rs33954632, TOPMed rs33954632, gnomAD rs33954632, REVEL 0.88, ESM-1b 1.00, Pathogenic, in Grange-blanche
- A28P (p.Ala28Pro), ExAC rs35424040, TOPMed rs35424040, gnomAD rs35424040, ESM-1b 1.00, AlphaMissense 0.98, Pathogenic, in Grange-blanche
- A28S (p.Ala28Ser), rs35424040, ClinGen CA124983, ClinVar RCV000016439, ClinVar RCV000016440, REVEL 0.64, ESM-1b 1.00, Pathogenic, Beta-thalassemia HBB/LCRB
- A28T (p.Ala28Thr), ExAC rs35424040, TOPMed rs35424040, gnomAD rs35424040, ESM-1b 0.51, AlphaMissense 0.16, Likely pathogenic, Beta-thalassemia HBB/LCRB
- A28V (p.Ala28Val), rs33954632, ClinGen CA124879, ClinVar RCV000016364, ClinVar RCV003441719, REVEL 0.78, ESM-1b 0.73, Uncertain significance, not provided
- A28A (p.Ala28Ala), rs748296717, gnomAD 11-5226938-G-T, CADD 11.70
- L29M (p.Leu29Met), rs33958088, ClinGen CA125460, ClinVar RCV000016835, TOPMed rs33958088, ESM-1b 0.53, AlphaMissense 0.62, other, HEMOGLOBIN CHILE
- L29P (p.Leu29Pro), rs33916412, ClinGen CA124877, ClinVar RCV000016362, ClinVar RCV000016363, ESM-1b 1.00, AlphaMissense 0.98, Pathogenic, Hemoglobinopathy
- L29Q (p.Leu29Gln), rs33916412, ClinGen CA125184, ClinVar RCV000016611, ClinVar RCV000016612, ESM-1b 1.00, AlphaMissense 0.98, Pathogenic; other, HEMOGLOBIN ST. LOUIS; Heinz body anemia
- L29R (p.Leu29Arg), rs33916412, ClinGen CA125352, ClinVar RCV000016751, Ensembl rs33916412, ESM-1b 1.00, AlphaMissense 0.95, other, HEMOGLOBIN CHESTERFIELD
- L29L (p.Leu29Leu), rs1191121382, gnomAD 11-5226935-C-A, CADD 10.10
- G30C (p.Gly30Cys), TOPMed rs33974277, gnomAD rs33974277, REVEL 0.61, ESM-1b 1.00
- G30D (p.Gly30Asp), rs35685286, ClinGen CA125003, NCI-TCGA Cosmic COSV5894, cosmic curated COSV58941, ESM-1b 1.00, AlphaMissense 0.98, Likely pathogenic, not provided
- G30S (p.Gly30Ser), rs33974277, ClinGen CA125534, cosmic curated COSV58941, ClinVar RCV000016882, REVEL 0.69, ESM-1b 0.86, other, HEMOGLOBIN TIZI-OUZOU
- G30G (p.Gly30Gly), rs35578002, gnomAD 11-5226932-G-A, CADD 24.50
- R31G (p.Arg31Gly), rs35684407, ClinGen CA217115065, ClinVar RCV001078278, ClinVar RCV005232121, ESM-1b 1.00, AlphaMissense 0.87, Pathogenic/Likely pathogenic, beta Thalassemia; not provided
- R31K (p.Arg31Lys), rs33960103, ClinGen CA342877, cosmic curated COSV58942, ClinVar RCV000030006, REVEL 0.90, ESM-1b 1.00, Likely pathogenic, METHEMOGLOBINEMIA, BETA TYPE; Heinz body anemia; Beta-thalassemia HBB/LCRB
- R31S (p.Arg31Ser), rs1135071, ClinGen CA125196, ClinVar RCV000016619, ClinVar RCV000016620, REVEL 0.95, ESM-1b 1.00, Pathogenic, beta Thalassemia
- R31T (p.Arg31Thr), rs33960103, ClinGen CA213890, cosmic curated COSV58942, ClinVar RCV000016432, REVEL 0.94, ESM-1b 1.00, Pathogenic, Beta-thalassemia HBB/LCRB; Erythrocytosis, familial, 6; Heinz body anemia
- R31R (p.Arg31Arg), rs1135071, gnomAD 11-5226799-C-T, CADD 15.80, SIFT 0.00
- L32P (p.Leu32Pro), rs33920173, ClinGen CA125243, ClinVar RCV000016647, UniProt VAR 002915, ESM-1b 1.00, AlphaMissense 0.99, other, HEMOGLOBIN YOKOHAMA
- L32R (p.Leu32Arg), rs33920173, ClinGen CA217114670, ClinVar RCV000016810, Ensembl rs33920173, ESM-1b 1.00, AlphaMissense 0.97, other, HEMOGLOBIN HAKKARI
- L32V (p.Leu32Val), rs33956555, ClinGen CA125372, ClinVar RCV000016771, ExAC rs33956555, ESM-1b 1.00, AlphaMissense 0.36, other, HEMOGLOBIN MUSCAT
- L32L (p.Leu32Leu), rs778841729, gnomAD 11-5226796-C-T, CADD 8.82, SIFT 1.00
- L33P (p.Leu33Pro), rs33948578, ClinGen CA125096, ClinVar RCV000016546, ClinVar RCV000016547, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic, not provided
- L33Q (p.Leu33Gln), rs33948578, ClinGen CA037802, ClinVar RCV000016807, ClinVar RCV001811076, ESM-1b 1.00, AlphaMissense 0.98, Likely pathogenic, not provided
- L33R (p.Leu33Arg), rs33948578, ClinGen CA124785, ClinVar RCV000016295, UniProt VAR 002916, ESM-1b 1.00, AlphaMissense 0.97, other, HEMOGLOBIN CASTILLA
Public HBB analysis runs
- HBB analysis run — HBB (775 variants) — completed 2026-05-15