CALCB (P10092) variants and mutations
CALCB (also known as P10092) is a human protein-coding gene encoding a calcitonin gene-related peptide 2 protein. CGRP2 is a secreted peptide that activates the CALCRL-RAMP1 receptor complex. Like CGRP1, it promotes blood-vessel dilation and may contribute to signaling in the central nervous system. This analysis covers 358 CALCB variants and mutations. Of these, 84% have computational variant effect predictions. Disease context includes migraine disorder, Increased circulating prolactin concentration, and hyperprolactinemia. Example CALCB variants include G2A, G2S, and G2G.
Variant analysis overview
- Gene: CALCB
- Protein: P10092
- UniProt accession: P10092
- Organism: Homo sapiens
- Variants analyzed: 358
- Variant scope: all variants
- Completed: 2026-07-24
Variant and mutation evidence
- Variant composition: 181 unspecified-consequence records; 10 frameshift variants; 87 missense variants; 71 synonymous variants; 4 stop-gained variants; 1 splice-region variants; 2 in-frame deletions; 1 stop lost; 1 substitution
- Prediction scores: 300 variants have prediction scores (84% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: migraine disorder, Increased circulating prolactin concentration, hyperprolactinemia, diverticular disease, Cluster headache, diverticulitis, digestive system disorder, abdominal abscess, respiratory tract infectious disorder, alcohol drinking, interstitial cystitis, diabetic polyneuropathy.
Protein structure and variant hotspots
- Protein features: 1 post-translational modification sites.
- PTM context: 1 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable CALCB variants
Examples include G2A, G2S, G2G, G2R, G2D, F3Y, F3S, F3F. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- G2A (p.Gly2Ala), ExAC rs776318498, gnomAD rs776318498, REVEL 0.14, CADD 20.20
- G2S (p.Gly2Ser), Ensembl rs1850377600, REVEL 0.18, CADD 25.40
- G2G (p.Gly2Gly), gnomAD 11-15074715-C-T, CADD 16.70
- G2R (p.Gly2Arg), rs1249437039, gnomAD 11-15074716-G-C, CADD 8.96
- G2D (p.Gly2Asp), gnomAD 11-15074717-G-A, CADD 11.00
- F3Y (p.Phe3Tyr), ExAC rs761441692, gnomAD rs761441692, REVEL 0.14, CADD 28.70
- F3S (p.Phe3Ser), gnomAD 11-15074726-T-C, REVEL 0.19, CADD 26.50
- F3F (p.Phe3Phe), rs1055368526, gnomAD 11-15074727-C-T, CADD 12.50
- R4Q (p.Arg4Gln), rs770182897, NCI-TCGA Cosmic COSV6083, cosmic curated COSV60834, ExAC rs770182897, REVEL 0.07, CADD 21.90, Variant assessed as somatic; moderate impact.
- R4G (p.Arg4Gly), rs768103547, gnomAD 11-15074710-A-G, CADD 13.80
- R4K (p.Arg4Lys), gnomAD 11-15074711-G-A, CADD 17.60
- R4W (p.Arg4Trp), gnomAD 11-15074728-C-T, REVEL 0.17, CADD 13.80
- R4R (p.Arg4Arg), gnomAD 11-15074730-G-C, CADD 14.40
- K5Q (p.Lys5Gln), gnomAD 11-14978339-A-C, CADD 9.60
- K5K (p.Lys5Lys), gnomAD 11-14978344-A-G, CADD 0.88
- K5E (p.Lys5Glu), rs773557900, gnomAD 11-15074728-C-CG, CADD 29.00
- F6L (p.Phe6Leu), ExAC rs773655356, TOPMed rs773655356, gnomAD rs773655356, REVEL 0.03, CADD 21.30
- F6F (p.Phe6Phe), rs773655356, gnomAD 11-15074736-C-T, CADD 15.10
- S7F (p.Ser7Phe), ExAC rs763415957, gnomAD rs763415957, REVEL 0.10, CADD 21.20
- S7Y (p.Ser7Tyr), gnomAD 11-15074738-C-A, REVEL 0.29, CADD 24.00
- S7S (p.Ser7Ser), rs766953127, gnomAD 11-15074739-C-T, CADD 9.37
- P8H (p.Pro8His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P8L (p.Pro8Leu), 1000Genomes rs529327624, ExAC rs529327624, TOPMed rs529327624, gnomAD rs529327624, REVEL 0.06, CADD 20.00, Uncertain significance, not specified
- P8S (p.Pro8Ser), TOPMed rs1336814260, gnomAD rs1336814260, REVEL 0.04, CADD 16.30
- P8R (p.Pro8Arg), gnomAD 11-15074741-C-G, REVEL 0.10, CADD 22.70
- P8P (p.Pro8Pro), rs1273177759, gnomAD 11-15074742-C-G, CADD 10.40
- F9L (p.Phe9Leu), Ensembl rs1175869819
- F9S (p.Phe9Ser), NCI-TCGA TCGA novel, REVEL 0.21, CADD 25.40, Variant assessed as somatic; high impact.
- F9V (p.Phe9Val), gnomAD 11-15074743-T-G, REVEL 0.25, CADD 25.50
- L10F (p.Leu10Phe), rs1849704285, gnomAD 11-14978354-C-T, CADD 5.93
- L10P (p.Leu10Pro), gnomAD 11-14978355-T-C, CADD 15.80
- L10L (p.Leu10Leu), rs1850377986, gnomAD 11-15074746-C-T, CADD 12.10
- A11V (p.Ala11Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A11S (p.Ala11Ser), gnomAD 11-14978348-G-T, CADD 0.22
- A11T (p.Ala11Thr), rs1849704210, gnomAD 11-14978348-G-A, CADD 0.53
- A11D (p.Ala11Asp), gnomAD 11-14978349-C-A, CADD 9.38
- A11G (p.Ala11Gly), rs574877649, gnomAD 11-14978349-C-G, CADD 3.67
- A11A (p.Ala11Ala), rs1849704240, gnomAD 11-14978350-T-A, CADD 5.13
- L12F (p.Leu12Phe), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10015, Variant assessed as somatic; moderate impact.
- L12I (p.Leu12Ile), NCI-TCGA Cosmic COSV1001, Variant assessed as somatic; moderate impact.
- L12V (p.Leu12Val), gnomAD 11-15074752-C-G, REVEL 0.04, CADD 16.30
- L12R (p.Leu12Arg), gnomAD 11-15074753-T-G, REVEL 0.28, CADD 29.50
- L12L (p.Leu12Leu), rs759637036, gnomAD 11-15074754-C-T, CADD 14.20
- S13N (p.Ser13Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S13S (p.Ser13Ser), rs1850378038, gnomAD 11-15074757-T-C, CADD 15.40
- I14M (p.Ile14Met), ExAC rs767532661, TOPMed rs767532661, gnomAD rs767532661
- I14V (p.Ile14Val), gnomAD 11-15074758-A-G, REVEL 0.09, CADD 16.50
- I14I (p.Ile14Ile), rs767532661, gnomAD 11-15074760-C-T, CADD 14.50
- L15S (p.Leu15Ser), gnomAD 11-15074760-CTTGG, CADD 32.00
- L15L (p.Leu15Leu), gnomAD 11-15074761-T-C, CADD 15.10
- V16F (p.Val16Phe), gnomAD rs1255798853, REVEL 0.21, CADD 23.90
- V16V (p.Val16Val), rs1850378108, gnomAD 11-15074766-C-T, CADD 14.80
- L17M (p.Leu17Met), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10015, Variant assessed as somatic; moderate impact.
- L17P (p.Leu17Pro), ExAC rs752957836, gnomAD rs752957836, REVEL 0.41, CADD 32.00
- L17L (p.Leu17Leu), gnomAD 11-15074769-G-C, CADD 11.60
- Y18C (p.Tyr18Cys), ExAC rs756345561, gnomAD rs756345561, REVEL 0.06, CADD 22.30
- Y18S (p.Tyr18Ser), ExAC rs756345561, gnomAD rs756345561
- Y18* (p.Tyr18Ter), gnomAD 11-15074772-C-G, CADD 36.00
- Y18Y (p.Tyr18Tyr), gnomAD 11-15074772-C-T, CADD 12.70
- Q19K (p.Gln19Lys), gnomAD 11-14978357-C-A, CADD 2.06
- Q19R (p.Gln19Arg), gnomAD 11-15074774-A-G, REVEL 0.20, CADD 26.30
- Q19H (p.Gln19His), gnomAD 11-15074775-G-T, REVEL 0.10, CADD 23.20
- A20T (p.Ala20Thr), TOPMed rs980235610, gnomAD rs980235610, REVEL 0.13, CADD 23.00
- A20P (p.Ala20Pro), gnomAD 11-15074776-G-C, REVEL 0.27, CADD 27.30
- A20A (p.Ala20Ala), rs139794988, gnomAD 11-15074778-G-A, CADD 6.51
- G21A (p.Gly21Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G21D (p.Gly21Asp), gnomAD 11-15074780-G-A, REVEL 0.09, CADD 22.40
- G21G (p.Gly21Gly), gnomAD 11-15074781-C-T, CADD 15.50
- S22R (p.Ser22Arg), gnomAD rs1167372632, REVEL 0.08, CADD 21.00
- S22T (p.Ser22Thr), gnomAD 11-15074783-G-C, REVEL 0.09, CADD 21.60
- S22I (p.Ser22Ile), gnomAD 11-15074783-G-T, REVEL 0.07, CADD 22.40
- L23L (p.Leu23Leu), rs376322094, gnomAD 11-15074787-C-T, CADD 13.90
- Q24L (p.Gln24Leu), 1000Genomes rs369719079, ExAC rs369719079, TOPMed rs369719079, gnomAD rs369719079, Uncertain significance
- Q24R (p.Gln24Arg), rs369719079, ClinGen CA5897045, ClinVar RCV004287122, 1000Genomes rs369719079, REVEL 0.14, CADD 26.00, Uncertain significance, not specified
- Q24E (p.Gln24Glu), gnomAD 11-15074788-C-G, REVEL 0.07, CADD 23.20
- Q24P (p.Gln24Pro), gnomAD 11-15074789-A-C, REVEL 0.12, CADD 23.90
- A25E (p.Ala25Glu), cosmic curated COSV60834, TOPMed rs1311329522, gnomAD rs1311329522, REVEL 0.35, CADD 24.80
- A25V (p.Ala25Val), TOPMed rs1311329522, gnomAD rs1311329522
- A25T (p.Ala25Thr), gnomAD 11-15074791-G-A, REVEL 0.29, CADD 31.00
- A26V (p.Ala26Val), ExAC rs779948872, gnomAD rs779948872, REVEL 0.02, CADD 22.40
- A26G (p.Ala26Gly), gnomAD 11-15074795-C-G, REVEL 0.11, CADD 26.40
- A26E (p.Ala26Glu), gnomAD 11-15074795-C-A, REVEL 0.18, CADD 24.90
- A26A (p.Ala26Ala), gnomAD 11-15074796-G-A, CADD 8.86
- P27L (p.Pro27Leu), gnomAD rs1396405869, REVEL 0.44, CADD 31.00
- P27S (p.Pro27Ser), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10015, Variant assessed as somatic; moderate impact.
- P27T (p.Pro27Thr), gnomAD 11-15074797-C-A, REVEL 0.40, CADD 25.60
- P27Q (p.Pro27Gln), gnomAD 11-15074798-C-A, REVEL 0.35, CADD 28.90
- P27P (p.Pro27Pro), gnomAD 11-15074799-A-G, CADD 13.90
- F28L (p.Phe28Leu), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10015, Variant assessed as somatic; moderate impact.
- F28S (p.Phe28Ser), rs1393895916, gnomAD 11-15074799-AT-A, CADD 25.70
- R29S (p.Arg29Ser), 1000Genomes rs541439036, ExAC rs541439036, TOPMed rs541439036, gnomAD rs541439036, REVEL 0.35, CADD 24.10, Likely benign
- R29W (p.Arg29Trp), ExAC rs746992399, gnomAD rs746992399, REVEL 0.54, CADD 34.00
- R29R (p.Arg29Arg), rs746992399, gnomAD 11-15074803-A-C, CADD 23.20
- R29T (p.Arg29Thr), gnomAD 11-15074804-G-C, REVEL 0.45, CADD 36.00
- S30F (p.Ser30Phe), ExAC rs772389365, gnomAD rs772389365, REVEL 0.16, CADD 23.50
- A31D (p.Ala31Asp), cosmic curated COSV60834
- A31T (p.Ala31Thr), cosmic curated COSV60834
- A31V (p.Ala31Val), TOPMed rs1361777863, gnomAD rs1361777863, REVEL 0.06, CADD 10.90
- L32A (p.Leu32Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L32M (p.Leu32Met), NCI-TCGA Cosmic COSV6083, cosmic curated COSV60834, Variant assessed as somatic; moderate impact.
- L32L (p.Leu32Leu), rs1212577945, gnomAD 11-15075068-C-T, CADD 6.08
- L32P (p.Leu32Pro), gnomAD 11-15075069-T-C, REVEL 0.41, CADD 27.40
- E33* (p.Glu33Ter), TOPMed rs1043867993, gnomAD rs1043867993, CADD 41.00
- E33D (p.Glu33Asp), NCI-TCGA Cosmic COSV6083, cosmic curated COSV60834, Variant assessed as somatic; moderate impact.
- E33R (p.Glu33Arg), gnomAD 11-14978338-GA-G, CADD 16.30
- E33Q (p.Glu33Gln), gnomAD 11-14978345-G-C, CADD 1.94
- E33G (p.Glu33Gly), rs892894194, gnomAD 11-14978346-A-G, CADD 5.77
- E33E (p.Glu33Glu), rs1555027555, gnomAD 11-14978347-G-A, CADD 0.24
- S34G (p.Ser34Gly), NCI-TCGA Cosmic COSV6083, cosmic curated COSV60834, Variant assessed as somatic; moderate impact.
- S34R (p.Ser34Arg), rs776091672, ClinGen CA379871724, ClinVar RCV004434490, ExAC rs776091672, REVEL 0.03, CADD 23.80, Uncertain significance, not specified
- S34I (p.Ser34Ile), gnomAD 11-15075075-G-T, REVEL 0.07, CADD 24.20
- S34S (p.Ser34Ser), rs776091672, gnomAD 11-15075076-C-T, CADD 12.00
- S35G (p.Ser35Gly), Ensembl rs775991658
- P36Q (p.Pro36Gln), NCI-TCGA TCGA novel, REVEL 0.11, CADD 19.10, Variant assessed as somatic; moderate impact.
- P36T (p.Pro36Thr), cosmic curated COSV60834, TOPMed rs1267624517, gnomAD rs1267624517, REVEL 0.08, CADD 3.18
- P36A (p.Pro36Ala), gnomAD 11-15075080-C-G, REVEL 0.09, CADD 3.20
- P36P (p.Pro36Pro), gnomAD 11-15075082-A-G, CADD 5.99
- D37E (p.Asp37Glu), TOPMed rs934096451, gnomAD rs934096451, REVEL 0.08, CADD 14.30, Uncertain significance, not specified
- D37G (p.Asp37Gly), Ensembl rs1850381603, REVEL 0.29, CADD 23.80
- D37H (p.Asp37His), gnomAD 11-15075083-G-C, REVEL 0.50, CADD 26.40
- P38L (p.Pro38Leu), rs774903834, ClinGen CA5897077, ClinVar RCV004224939, ExAC rs774903834, REVEL 0.06, CADD 4.25, Uncertain significance, not specified
- P38Q (p.Pro38Gln), ExAC rs774903834, TOPMed rs774903834, gnomAD rs774903834, REVEL 0.06, CADD 4.84, Uncertain significance
- P38R (p.Pro38Arg), ExAC rs774903834, TOPMed rs774903834, gnomAD rs774903834, REVEL 0.07, CADD 2.56, Uncertain significance
- P38S (p.Pro38Ser), cosmic curated COSV60834, TOPMed rs1051094271, gnomAD rs1051094271, REVEL 0.09, CADD 8.87
- P38P (p.Pro38Pro), rs1377497958, gnomAD 11-15075088-G-A, CADD 0.92
- A39V (p.Ala39Val), TOPMed rs1850381788
- A39G (p.Ala39Gly), gnomAD 11-15075090-C-G, REVEL 0.06, CADD 10.10
- A39D (p.Ala39Asp), gnomAD 11-15075090-C-A, REVEL 0.07, CADD 15.40
- T40A (p.Thr40Ala), TOPMed rs1850381817, gnomAD rs1850381817, REVEL 0.04, CADD 3.34
- T40I (p.Thr40Ile), TOPMed rs942560861
- T40T (p.Thr40Thr), rs1438673634, gnomAD 11-15075094-A-C, CADD 2.39
- L41F (p.Leu41Phe), cosmic curated COSV10015, Ensembl rs1850381939, REVEL 0.09, CADD 16.40
- S42G (p.Ser42Gly), gnomAD rs1850381958, REVEL 0.07, CADD 15.50
- S42N (p.Ser42Asn), ExAC rs776832564, gnomAD rs776832564, REVEL 0.12, CADD 12.90
- S42S (p.Ser42Ser), rs143189175, gnomAD 11-15075100-T-C, CADD 8.56
- K43K (p.Lys43Lys), rs765460725, gnomAD 11-15075103-A-G, CADD 8.87
- E44* (p.Glu44Ter), cosmic curated COSV60834
- E44D (p.Glu44Asp), rs751247746, ClinGen CA5897082, ClinVar RCV004192578, ExAC rs751247746, REVEL 0.04, CADD 21.10, Uncertain significance, not specified
- E44G (p.Glu44Gly), rs376051795, ESP rs376051795, REVEL 0.15, CADD 25.30, Variant assessed as somatic; moderate impact.
- D45N (p.Asp45Asn), cosmic curated COSV60834
- D45D (p.Asp45Asp), rs61736643, gnomAD 11-15075109-C-T, CADD 9.37
- A46T (p.Ala46Thr), rs200666060, ClinGen CA5897084, ClinVar RCV004434491, ESP rs200666060, REVEL 0.12, CADD 22.80, Uncertain significance, not specified
- A46V (p.Ala46Val), ExAC rs752729119, gnomAD rs752729119, REVEL 0.04, CADD 18.40
- A46A (p.Ala46Ala), rs755654013, gnomAD 11-15075112-G-A, CADD 9.53
- L48F (p.Leu48Phe), ExAC rs777490359, gnomAD rs777490359, REVEL 0.18, CADD 25.80
- L48H (p.Leu48His), NCI-TCGA Cosmic COSV1001, NCI-TCGA Cosmic COSV6083, cosmic curated COSV60834, Variant assessed as somatic; moderate impact.
- L48P (p.Leu48Pro), rs1264892328, NCI-TCGA Cosmic COSV1001, cosmic curated COSV10015, NCI-TCGA Cosmic COSV6083, REVEL 0.28, CADD 29.90, Variant assessed as somatic; moderate impact.
- L48L (p.Leu48Leu), gnomAD 11-15075118-C-T, CADD 11.80
- L50R (p.Leu50Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L50del (p.Leu50del), gnomAD 11-15075114-GCCT-, CADD 20.10
- L50L (p.Leu50Leu), rs1193073799, gnomAD 11-15075124-G-A, CADD 12.70
- A51V (p.Ala51Val), NCI-TCGA Cosmic COSV1001, cosmic curated COSV10015, Variant assessed as somatic; moderate impact.
- A51A (p.Ala51Ala), rs748933844, gnomAD 11-15075127-T-A, CADD 13.50
- A52T (p.Ala52Thr), Ensembl rs1850382378
- A52V (p.Ala52Val), gnomAD 11-15075129-C-T, REVEL 0.19, CADD 25.50
- A52A (p.Ala52Ala), gnomAD 11-15075130-A-G, CADD 12.00
- L53P (p.Leu53Pro), cosmic curated COSV10740
- L53L (p.Leu53Leu), rs778709516, gnomAD 11-15075131-C-T, CADD 11.40
- L53Q (p.Leu53Gln), gnomAD 11-15075132-T-A, REVEL 0.37, CADD 29.80
- V54L (p.Val54Leu), TOPMed rs1850382480, REVEL 0.17, CADD 17.50
- Q55K (p.Gln55Lys), gnomAD rs1413967734
- Q55L (p.Gln55Leu), ESP rs372815579, TOPMed rs372815579, gnomAD rs372815579, REVEL 0.12, CADD 23.90
- Q55P (p.Gln55Pro), ESP rs372815579, TOPMed rs372815579, gnomAD rs372815579, REVEL 0.18, CADD 25.30
- D56E (p.Asp56Glu), TOPMed rs1164167951, gnomAD rs1164167951, REVEL 0.05, CADD 17.60
- D56H (p.Asp56His), Ensembl rs2133640625
- D56Y (p.Asp56Tyr), gnomAD 11-15075140-G-T, REVEL 0.16, CADD 24.60
- D56N (p.Asp56Asn), gnomAD 11-15075140-G-A, REVEL 0.08, CADD 21.20
- D56V (p.Asp56Val), gnomAD 11-15075141-A-T, REVEL 0.18, CADD 23.80
- D56D (p.Asp56Asp), rs1164167951, gnomAD 11-15075142-C-T, CADD 10.70
- Y57C (p.Tyr57Cys), ExAC rs772540926, gnomAD rs772540926, REVEL 0.17, CADD 26.20
- Y57Y (p.Tyr57Tyr), rs775832606, gnomAD 11-15075145-T-C, CADD 8.09
- Y57* (p.Tyr57Ter), gnomAD 11-15075145-T-A, CADD 36.00
- V58G (p.Val58Gly), gnomAD rs1372157338, REVEL 0.27, CADD 25.00
- V58L (p.Val58Leu), ExAC rs747622008, TOPMed rs747622008, gnomAD rs747622008, REVEL 0.07, CADD 19.50
- V58M (p.Val58Met), ExAC rs747622008, TOPMed rs747622008, gnomAD rs747622008, REVEL 0.01, CADD 20.20
- V58E (p.Val58Glu), gnomAD 11-15075147-T-A, REVEL 0.08, CADD 21.90
- V58A (p.Val58Ala), gnomAD 11-15075147-T-C, REVEL 0.12, CADD 21.60
- V58V (p.Val58Val), gnomAD 11-15075148-G-C, CADD 9.10
- Q59R (p.Gln59Arg), ExAC rs776636220, gnomAD rs776636220, REVEL 0.44, CADD 26.80
- M60I (p.Met60Ile), NCI-TCGA Cosmic COSV6083, cosmic curated COSV60834, REVEL 0.15, CADD 24.00, Variant assessed as somatic; moderate impact.
Public CALCB analysis runs
- CALCB analysis run — CALCB (358 variants) — completed 2026-07-24