FGB (Fibrinogen beta chain) variants and mutations
FGB (also known as Fibrinogen beta chain) is a human protein-coding gene encoding a fibrinogen beta chain protein. It contributes the beta chains required for assembly and secretion of functional fibrinogen and subsequent fibrin-clot formation. Pathogenic variants can reduce fibrinogen quantity or alter clot properties, producing bleeding, thrombosis, or both. This analysis covers 886 FGB variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes congenital afibrinogenemia, familial dysfibrinogenemia, and Familial afibrinogenemia. Example FGB variants include K2*, K2E, and K2R.
Variant analysis overview
- Gene: FGB
- Protein: Fibrinogen beta chain
- UniProt accession: P02675
- Organism: Homo sapiens
- Variants analyzed: 886
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 622 unspecified-consequence records; 12 frameshift variants; 145 missense variants; 84 synonymous variants; 9 stop-gained variants; 3 in-frame deletions; 3 splice-region variants; 2 in-frame insertions; 6 substitution
- Prediction scores: 678 variants have prediction scores (77% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: congenital afibrinogenemia, familial dysfibrinogenemia, Familial afibrinogenemia, congenital fibrinogen deficiency, familial hypodysfibrinogenemia, cancer, Noonan syndrome, Costello syndrome, hypertrophic cardiomyopathy, hemorrhage, Recurrent thrombophlebitis, deep vein thrombosis.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 post-translational modification sites.
- Structural context: 323 variants have structural context.
- PTM context: 6 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 FGB variants
Examples include K2*, K2E, K2R, K2I, K2K, K2N, R3S, R3K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- K2* (p.Lys2Ter), ESP rs6053, ExAC rs6053, TOPMed rs6053, gnomAD rs6053, CADD 34.00, Uncertain significance
- K2E (p.Lys2Glu), rs6053, ClinGen CA3114423, ClinVar RCV000307288, ClinVar RCV003556357, REVEL 0.15, CADD 11.10, Uncertain significance, Inborn genetic diseases; not provided; Congenital afibrinogenemia
- K2R (p.Lys2Arg), gnomAD 4-154563023-A-G, REVEL 0.11, CADD 15.80
- K2I (p.Lys2Ile), gnomAD 4-154563023-A-T, REVEL 0.08, CADD 20.60
- K2K (p.Lys2Lys), gnomAD 4-154563024-A-G, CADD 9.79
- K2N (p.Lys2Asn), gnomAD 4-154563024-A-T, REVEL 0.15, CADD 16.70
- R3S (p.Arg3Ser), gnomAD rs1446931019, REVEL 0.13, CADD 23.30
- R3K (p.Arg3Lys), gnomAD 4-154563021-G-GA, CADD 23.40
- R3G (p.Arg3Gly), gnomAD 4-154563021-GA-G, CADD 20.20
- R3T (p.Arg3Thr), gnomAD 4-154563026-G-C, REVEL 0.06, CADD 22.10
- R3M (p.Arg3Met), gnomAD 4-154563026-G-T, REVEL 0.19, CADD 24.30
- M4I (p.Met4Ile), Ensembl rs867253600, REVEL 0.10, CADD 18.40
- M4L (p.Met4Leu), rs767891657, ClinGen CA3114424, ClinVar RCV003854984, ExAC rs767891657, REVEL 0.09, CADD 13.70, Uncertain significance, not provided
- M4V (p.Met4Val), ExAC rs767891657, TOPMed rs767891657, gnomAD rs767891657, REVEL 0.10, CADD 14.10, Uncertain significance
- M4T (p.Met4Thr), gnomAD 4-154563029-T-C, REVEL 0.10, CADD 7.78
- M4K (p.Met4Lys), gnomAD 4-154563029-T-A, REVEL 0.05, CADD 9.31
- V5A (p.Val5Ala), TOPMed rs1730011162, REVEL 0.11, CADD 13.60
- V5F (p.Val5Phe), gnomAD 4-154563029-TG-T, CADD 22.40
- V5V (p.Val5Val), gnomAD 4-154563033-T-C, CADD 9.92
- S6C (p.Ser6Cys), ExAC rs752925190, gnomAD rs752925190, REVEL 0.08, CADD 22.60
- S6F (p.Ser6Phe), ExAC rs752925190, gnomAD rs752925190, REVEL 0.09, CADD 20.50
- S6P (p.Ser6Pro), rs1345315728, ClinGen CA358507408, ClinVar RCV003374086, gnomAD rs1345315728, AlphaMissense 0.10, MetaLR 0.11, Uncertain significance, Inborn genetic diseases
- S6Y (p.Ser6Tyr), ExAC rs752925190, gnomAD rs752925190, REVEL 0.09, CADD 22.50
- S6S (p.Ser6Ser), rs1425004470, gnomAD 4-154563036-T-C, CADD 11.30
- W7C (p.Trp7Cys), gnomAD rs1339198946, REVEL 0.14, CADD 23.70
- W7R (p.Trp7Arg), gnomAD rs1281486791, REVEL 0.09, CADD 23.70
- W7* (p.Trp7Ter), gnomAD 4-154563037-TG-T, CADD 28.60
- W7G (p.Trp7Gly), gnomAD 4-154563037-T-G, REVEL 0.15, CADD 22.80
- W7L (p.Trp7Leu), gnomAD 4-154563038-G-T, REVEL 0.06, CADD 25.30
- S8G (p.Ser8Gly), TOPMed rs1194557267, gnomAD rs1194557267, REVEL 0.03, CADD 18.60
- S8R (p.Ser8Arg), TOPMed rs1194557267, gnomAD rs1194557267, REVEL 0.02, CADD 21.40
- S8N (p.Ser8Asn), gnomAD 4-154563041-G-A, REVEL 0.06, CADD 9.90
- S8I (p.Ser8Ile), gnomAD 4-154563041-G-T, REVEL 0.04, CADD 20.00
- S8S (p.Ser8Ser), rs1275769193, gnomAD 4-154563042-C-T, CADD 9.32
- F9Y (p.Phe9Tyr), gnomAD 4-154563044-T-A, REVEL 0.10, CADD 22.80
- F9S (p.Phe9Ser), gnomAD 4-154563044-T-C, REVEL 0.13, CADD 22.40
- F9F (p.Phe9Phe), gnomAD 4-154563045-C-T, CADD 9.59
- F9L (p.Phe9Leu), gnomAD 4-154563045-C-A, REVEL 0.05, CADD 15.00
- H10Q (p.His10Gln), TOPMed rs1730012638, gnomAD rs1730012638, REVEL 0.09, CADD 6.70, Likely benign, Inborn genetic diseases
- H10R (p.His10Arg), gnomAD rs1012425059, REVEL 0.05, CADD 8.71
- H10Y (p.His10Tyr), gnomAD 4-154563046-C-T, REVEL 0.08, CADD 15.00
- H10N (p.His10Asn), gnomAD 4-154563046-C-A, REVEL 0.08, CADD 14.90
- H10H (p.His10His), rs1730012638, gnomAD 4-154563048-C-T, CADD 8.06
- K11E (p.Lys11Glu), ExAC rs756304323, gnomAD rs756304323, REVEL 0.07, CADD 21.30
- K11* (p.Lys11Ter), gnomAD 4-154563049-A-T, CADD 35.00
- K11R (p.Lys11Arg), gnomAD 4-154563050-A-G, REVEL 0.07, CADD 16.20
- K11I (p.Lys11Ile), gnomAD 4-154563050-A-T, REVEL 0.11, CADD 22.40
- K11K (p.Lys11Lys), gnomAD 4-154563051-A-G, CADD 3.47
- L12V (p.Leu12Val), ExAC rs777895153, TOPMed rs777895153, gnomAD rs777895153, REVEL 0.07, CADD 5.07, Uncertain significance, Inborn genetic diseases; not specified
- L12I (p.Leu12Ile), gnomAD 4-154563052-C-A, REVEL 0.07, CADD 6.98
- L12P (p.Leu12Pro), gnomAD 4-154563053-T-C, REVEL 0.05, CADD 19.10
- L12H (p.Leu12His), gnomAD 4-154563053-T-A, REVEL 0.04, CADD 18.10
- L12L (p.Leu12Leu), rs376146726, gnomAD 4-154563054-T-A, CADD 6.40
- K13N (p.Lys13Asn), gnomAD rs1194567458, REVEL 0.08, CADD 19.10
- K13del (p.Lys13del), gnomAD 4-154563054-TAAA-, CADD 17.70
- K13E (p.Lys13Glu), gnomAD 4-154563055-A-G, REVEL 0.04, CADD 12.20
- K13R (p.Lys13Arg), gnomAD 4-154563056-A-G, REVEL 0.09, CADD 23.30
- K13I (p.Lys13Ile), gnomAD 4-154563056-A-T, REVEL 0.08, CADD 23.90
- K13T (p.Lys13Thr), gnomAD 4-154563056-A-C, REVEL 0.10, CADD 22.20
- T14P (p.Thr14Pro), Ensembl rs1578780254, REVEL 0.09, CADD 23.60
- T14S (p.Thr14Ser), gnomAD 4-154563058-A-T, REVEL 0.08, CADD 20.40
- T14A (p.Thr14Ala), gnomAD 4-154563058-A-G, REVEL 0.10, CADD 21.30
- T14I (p.Thr14Ile), gnomAD 4-154563059-C-T, REVEL 0.06, CADD 12.60
- T14N (p.Thr14Asn), gnomAD 4-154563059-C-A, REVEL 0.06, CADD 12.80
- T14T (p.Thr14Thr), rs1377967103, gnomAD 4-154563060-C-T, CADD 12.30
- M15I (p.Met15Ile), TOPMed rs1442111279, REVEL 0.20, CADD 27.20
- M15V (p.Met15Val), gnomAD 4-154563061-A-G, REVEL 0.18, CADD 24.50
- M15T (p.Met15Thr), gnomAD 4-154563062-T-C, REVEL 0.16, CADD 25.40
- M15K (p.Met15Lys), gnomAD 4-154563062-T-A, REVEL 0.25, CADD 26.10
- K16E (p.Lys16Glu), TOPMed rs1254302693, REVEL 0.09, CADD 24.00
- K16* (p.Lys16Ter), gnomAD 4-154563064-A-T, CADD 37.00
- K16R (p.Lys16Arg), gnomAD 4-154563065-A-G, REVEL 0.04, CADD 18.80
- K16K (p.Lys16Lys), gnomAD 4-154563066-A-G, CADD 9.26
- H17Y (p.His17Tyr), gnomAD 4-154563067-C-T, REVEL 0.05, CADD 10.30
- H17N (p.His17Asn), gnomAD 4-154563067-C-A, REVEL 0.03, CADD 14.20
- H17L (p.His17Leu), gnomAD 4-154563068-A-T, REVEL 0.05, CADD 13.70
- L18P (p.Leu18Pro), gnomAD rs1166051982, REVEL 0.28, CADD 27.40
- L18L (p.Leu18Leu), gnomAD 4-154563070-C-T, CADD 12.80
- L18I (p.Leu18Ile), gnomAD 4-154563070-C-A, REVEL 0.09, CADD 23.10
- L18Q (p.Leu18Gln), gnomAD 4-154563071-T-A, REVEL 0.24, CADD 26.70
- L19F (p.Leu19Phe), Ensembl rs1175327788
- L19I (p.Leu19Ile), gnomAD 4-154563073-T-A, REVEL 0.04, CADD 17.30
- L19L (p.Leu19Leu), gnomAD 4-154563073-T-C, CADD 8.62
- L19S (p.Leu19Ser), gnomAD 4-154563074-T-C, REVEL 0.05, CADD 20.40
- p.Leu20 Leu23del, gnomAD 4-154563069-TCTAT, CADD 18.50
- L20M (p.Leu20Met), gnomAD 4-154563076-T-A, REVEL 0.18, CADD 19.40
- L20L (p.Leu20Leu), rs1398578995, gnomAD 4-154563076-T-C, CADD 6.74
- L20F (p.Leu20Phe), gnomAD 4-154563077-TG-T, CADD 25.40
- L21I (p.Leu21Ile), NCI-TCGA Cosmic COSV1001, REVEL 0.14, CADD 18.20, Variant assessed as somatic; moderate impact.
- L21V (p.Leu21Val), gnomAD 4-154563079-C-G, REVEL 0.13, CADD 17.70
- L21L (p.Leu21Leu), gnomAD 4-154563079-C-T, CADD 11.00
- L21H (p.Leu21His), gnomAD 4-154563079-CT-C, CADD 26.60
- L21P (p.Leu21Pro), gnomAD 4-154563080-T-C, REVEL 0.20, CADD 26.70
- L22I (p.Leu22Ile), TOPMed rs1465640449, gnomAD rs1465640449, REVEL 0.17, CADD 23.10
- L22P (p.Leu22Pro), TOPMed rs1200625532, gnomAD rs1200625532, REVEL 0.33, CADD 26.00
- L22L (p.Leu22Leu), rs1465640449, gnomAD 4-154563082-C-T, CADD 9.85
- L23L (p.Leu23Leu), rs1368231341, gnomAD 4-154563085-T-C, CADD 5.87
- L23S (p.Leu23Ser), gnomAD 4-154563085-T-TCA, CADD 24.40
- L23* (p.Leu23Ter), gnomAD 4-154563086-T-A, CADD 36.00
- C24Y (p.Cys24Tyr), Ensembl rs1028131034, REVEL 0.34, CADD 25.10
- C24R (p.Cys24Arg), gnomAD 4-154563088-T-C, REVEL 0.38, CADD 25.40
- C24S (p.Cys24Ser), gnomAD 4-154563088-T-A, REVEL 0.36, CADD 24.70
- C24F (p.Cys24Phe), gnomAD 4-154563089-G-T, REVEL 0.35, CADD 25.30
- C24C (p.Cys24Cys), gnomAD 4-154563090-T-C, CADD 11.90
- V25A (p.Val25Ala), TOPMed rs1258637928, REVEL 0.11, CADD 15.20
- V25I (p.Val25Ile), TOPMed rs1730015675, REVEL 0.04, CADD 15.20
- V25G (p.Val25Gly), gnomAD 4-154563092-T-G, REVEL 0.20, CADD 19.90
- V25V (p.Val25Val), gnomAD 4-154563093-T-C, CADD 8.98
- F26Y (p.Phe26Tyr), gnomAD 4-154563095-T-A, REVEL 0.07, CADD 2.36
- F26F (p.Phe26Phe), gnomAD 4-154563096-T-C, CADD 8.26
- L27* (p.Leu27Ter), NCI-TCGA TCGA novel, CADD 22.70, Variant assessed as somatic; high impact.
- L27P (p.Leu27Pro), rs1442627097, ClinGen CA358507657, ClinVar RCV001147193, ClinVar RCV006372152, REVEL 0.11, CADD 16.50, Uncertain significance, not provided; Inborn genetic diseases; Congenital afibrinogenemia
- L27S (p.Leu27Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L27L (p.Leu27Leu), gnomAD 4-154563097-C-T, CADD 3.50
- L27I (p.Leu27Ile), gnomAD 4-154563097-C-A, REVEL 0.08, CADD 0.29
- L27Q (p.Leu27Gln), gnomAD 4-154563098-T-A, REVEL 0.10, CADD 16.00
- V28I (p.Val28Ile), gnomAD 4-154563100-G-A, REVEL 0.03, CADD 8.30
- V28F (p.Val28Phe), gnomAD 4-154563100-G-T, REVEL 0.07, CADD 15.60
- V28A (p.Val28Ala), gnomAD 4-154563101-T-C, REVEL 0.04, CADD 12.60
- V28D (p.Val28Asp), gnomAD 4-154563101-T-A, REVEL 0.20, CADD 18.70
- V28V (p.Val28Val), rs375340782, gnomAD 4-154563102-T-C, CADD 7.32
- K29* (p.Lys29Ter), Ensembl rs2110750872, CADD 34.00
- K29R (p.Lys29Arg), ExAC rs746963310, gnomAD rs746963310, REVEL 0.03, CADD 8.63
- K29M (p.Lys29Met), gnomAD 4-154563104-A-T, REVEL 0.12, CADD 13.40
- K29K (p.Lys29Lys), rs1253547201, gnomAD 4-154563105-G-A, CADD 0.54
- K29N (p.Lys29Asn), gnomAD 4-154563105-G-T, REVEL 0.04, CADD 0.41
- S30F (p.Ser30Phe), Ensembl rs1730016704, REVEL 0.09, CADD 16.10
- S30T (p.Ser30Thr), gnomAD 4-154563106-T-A, REVEL 0.03, CADD 3.15
- S30P (p.Ser30Pro), gnomAD 4-154563106-T-C, REVEL 0.24, CADD 8.84
- S30Y (p.Ser30Tyr), gnomAD 4-154563107-C-A, REVEL 0.15, CADD 15.80
- S30S (p.Ser30Ser), gnomAD 4-154563108-C-A, CADD 1.39
- Q31K (p.Gln31Lys), Ensembl rs867036869, REVEL 0.07, CADD 3.79
- Q31R (p.Gln31Arg), rs2530757532, ClinGen CA358507698, ClinVar RCV002841500, REVEL 0.06, CADD 10.90, Uncertain significance, Inborn genetic diseases
- Q31* (p.Gln31Ter), gnomAD 4-154563109-C-T, CADD 28.50
- Q31H (p.Gln31His), gnomAD 4-154563111-A-C, REVEL 0.10, CADD 8.99
- Q31Q (p.Gln31Gln), rs1730016973, gnomAD 4-154563111-A-G, CADD 4.32
- G32D (p.Gly32Asp), NCI-TCGA TCGA novel, REVEL 0.03, CADD 0.00, Variant assessed as somatic; moderate impact.
- G32S (p.Gly32Ser), TOPMed rs1340697323, gnomAD rs1340697323, REVEL 0.05, CADD 7.06
- G32C (p.Gly32Cys), gnomAD 4-154563112-G-T, REVEL 0.14, CADD 11.60
- G32A (p.Gly32Ala), gnomAD 4-154563113-G-C, REVEL 0.07, CADD 0.00
- G32V (p.Gly32Val), gnomAD 4-154563113-G-T, REVEL 0.07, CADD 0.00
- G32G (p.Gly32Gly), gnomAD 4-154563114-T-A, CADD 1.66
- V33I (p.Val33Ile), 1000Genomes rs562142566, ExAC rs562142566, gnomAD rs562142566, REVEL 0.05, CADD 0.01, Uncertain significance, Inborn genetic diseases
- V33C (p.Val33Cys), gnomAD 4-154563113-G-GC, CADD 15.80
- V33D (p.Val33Asp), gnomAD 4-154563116-T-A, REVEL 0.08, CADD 0.00
- V33V (p.Val33Val), gnomAD 4-154563117-C-A, CADD 1.28
- N34D (p.Asn34Asp), rs2530757606, ClinGen CA358507727, ClinVar RCV002777780, REVEL 0.16, CADD 3.90, Likely benign, Inborn genetic diseases
- N34H (p.Asn34His), gnomAD 4-154563118-A-C, REVEL 0.15, CADD 9.04
- N34S (p.Asn34Ser), gnomAD 4-154563119-A-G, REVEL 0.14, CADD 6.13
- N34N (p.Asn34Asn), rs780849917, gnomAD 4-154563120-C-T, CADD 5.63
- N34K (p.Asn34Lys), gnomAD 4-154563120-C-A, REVEL 0.05, CADD 2.57
- D35G (p.Asp35Gly), TOPMed rs774271682, gnomAD rs774271682, REVEL 0.16, CADD 13.10
- D35N (p.Asp35Asn), rs747783086, ClinGen CA3114434, ClinVar RCV001147194, ClinVar RCV003283997, REVEL 0.10, CADD 10.10, Uncertain significance, Congenital afibrinogenemia; Inborn genetic diseases
- D35Y (p.Asp35Tyr), gnomAD 4-154563121-G-T, REVEL 0.10, CADD 9.78
- D35D (p.Asp35Asp), gnomAD 4-154563123-C-T, CADD 4.17
- D35E (p.Asp35Glu), gnomAD 4-154563123-C-A, REVEL 0.12, CADD 4.10
- N36D (p.Asn36Asp), gnomAD 4-154563124-A-G, REVEL 0.09, CADD 7.70
- N36S (p.Asn36Ser), gnomAD 4-154563125-A-G, REVEL 0.14, CADD 8.55
- N36N (p.Asn36Asn), rs1427655683, gnomAD 4-154563126-T-C, CADD 0.52
- N36K (p.Asn36Lys), gnomAD 4-154563126-T-A, REVEL 0.02, CADD 0.31
- E37G (p.Glu37Gly), gnomAD rs1374660969, REVEL 0.06, CADD 18.60
- E37K (p.Glu37Lys), rs769395119, ExAC rs769395119, gnomAD rs769395119, REVEL 0.06, CADD 4.05, Variant assessed as somatic; moderate impact.
- E37* (p.Glu37Ter), gnomAD 4-154563127-G-T, CADD 28.20
- E37E (p.Glu37Glu), rs1014952338, gnomAD 4-154563129-G-A, CADD 0.18
- E37D (p.Glu37Asp), gnomAD 4-154563129-G-T, REVEL 0.09, CADD 0.00
- E38D (p.Glu38Asp), rs1339535578, ClinGen CA358507784, ClinVar RCV003400388, REVEL 0.21, CADD 28.50, Uncertain significance, FGB-related disorder
- E38R (p.Glu38Arg), gnomAD 4-154563128-AG-A, CADD 4.83
- E38* (p.Glu38Ter), gnomAD 4-154563130-G-T, CADD 33.00
- E38K (p.Glu38Lys), gnomAD 4-154563130-G-A, REVEL 0.21, CADD 0.73
- E38E (p.Glu38Glu), rs1339535578, gnomAD 4-154563132-G-A, CADD 24.20
- G39D (p.Gly39Asp), rs1560816739, NCI-TCGA Cosmic COSV5741, Ensembl rs1560816739, AlphaMissense 0.06, MetaLR 0.05, Variant assessed as somatic; moderate impact.
- G39S (p.Gly39Ser), gnomAD 4-154565808-G-A, REVEL 0.11, CADD 0.00
- F40L (p.Phe40Leu), TOPMed rs1730130537
- F41L (p.Phe41Leu), gnomAD 4-154565814-T-C, REVEL 0.19, CADD 0.00
- F41F (p.Phe41Phe), rs770388453, gnomAD 4-154565816-C-T, CADD 2.47
- S42G (p.Ser42Gly), TOPMed rs1730130853, REVEL 0.11, CADD 0.16
- S42N (p.Ser42Asn), ExAC rs773855571, TOPMed rs773855571, gnomAD rs773855571, REVEL 0.07, AlphaMissense 0.08, Uncertain significance
- S42T (p.Ser42Thr), rs773855571, ClinGen CA358508247, ClinVar RCV002766704, ExAC rs773855571, AlphaMissense 0.08, MetaLR 0.05, Uncertain significance, not provided
- S42R (p.Ser42Arg), gnomAD 4-154565819-T-G, REVEL 0.07, CADD 16.40
- S42S (p.Ser42Ser), gnomAD 4-154565819-T-C, CADD 5.45
Public FGB analysis runs
- FGB analysis run — FGB (886 variants) — completed 2026-08-19