CALCA (P06881) variants and mutations
CALCA (also known as P06881) is a human protein-coding gene encoding a calcitonin gene-related peptide 1 protein. CGRP1 is a secreted peptide hormone that widens blood vessels through the CALCRL-RAMP1 receptor complex. CGRP1 is also abundant in the nervous system, where it can act as a neurotransmitter or neuromodulator. This analysis covers 404 CALCA variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes migraine disorder, AL amyloidosis, and hyperprolactinemia. Example CALCA variants include M1R, G2R, and G2S.
Variant analysis overview
- Gene: CALCA
- Protein: P06881
- UniProt accession: P06881
- Organism: Homo sapiens
- Variants analyzed: 404
- Variant scope: all variants
- Completed: 2026-07-24
Variant and mutation evidence
- Variant composition: 181 unspecified-consequence records; 2 stop lost; 2 stop retained variant; 72 synonymous variants; 109 missense variants; 24 frameshift variants; 4 in-frame deletions; 6 stop-gained variants; 2 in-frame insertions; 2 substitution
- Prediction scores: 348 variants have prediction scores (86% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: migraine disorder, AL amyloidosis, hyperprolactinemia, Increased circulating prolactin concentration, Cluster headache, COVID-19, neurodegenerative disease, diverticular disease, Sepsis, infection, neoplasm, medullary thyroid gland carcinoma.
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, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable CALCA variants
Examples include M1R, G2R, G2S, G2A, G2G, G2D, F3L, Q4H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1R (p.Met1Arg), rs782758761, []
- G2R (p.Gly2Arg), rs34587547, UniProt VAR 025271, 1000Genomes rs34587547, ESP rs34587547, REVEL 0.17, CADD 23.90
- G2S (p.Gly2Ser), 1000Genomes rs34587547, ESP rs34587547, ExAC rs34587547, TOPMed rs34587547, REVEL 0.13, CADD 18.80
- G2A (p.Gly2Ala), rs1849595663, gnomAD 11-14971187-GC-G, CADD 25.20
- G2G (p.Gly2Gly), rs1389889159, gnomAD 11-14971187-G-A, CADD 9.75
- G2D (p.Gly2Asp), gnomAD 11-14971188-C-T, REVEL 0.13, CADD 24.30
- F3L (p.Phe3Leu), gnomAD 11-14971186-A-G, REVEL 0.05, CADD 21.80
- Q4H (p.Gln4His), gnomAD 11-14971181-T-G, REVEL 0.06, CADD 14.80
- K5E (p.Lys5Glu), gnomAD rs1555026453, REVEL 0.41, CADD 26.10
- K5M (p.Lys5Met), gnomAD rs1555026452, REVEL 0.46, CADD 27.10
- K5N (p.Lys5Asn), ExAC rs782320394, gnomAD rs782320394, REVEL 0.35, CADD 23.00
- K5K (p.Lys5Lys), gnomAD 11-14971178-C-T, CADD 10.60
- K5R (p.Lys5Arg), gnomAD 11-14971179-T-C, REVEL 0.36, CADD 25.80
- F6L (p.Phe6Leu), ESP rs375202775, ExAC rs375202775, TOPMed rs375202775, gnomAD rs375202775, REVEL 0.06, CADD 19.30
- F6F (p.Phe6Phe), gnomAD 11-14971175-G-A, CADD 8.15
- S7C (p.Ser7Cys), ExAC rs781962903, TOPMed rs781962903, gnomAD rs781962903, REVEL 0.25, CADD 23.00
- S7F (p.Ser7Phe), rs781962903, NCI-TCGA Cosmic COSV1005, NCI-TCGA Cosmic COSV5902, cosmic curated COSV59028, REVEL 0.15, CADD 16.70, Variant assessed as somatic; moderate impact.
- S7S (p.Ser7Ser), rs782397226, gnomAD 11-14971172-G-A, CADD 5.88
- P8L (p.Pro8Leu), NCI-TCGA TCGA novel, Ensembl rs1313275155, Variant assessed as somatic; moderate impact.
- P8R (p.Pro8Arg), Ensembl rs1313275155
- P8del (p.Pro8del), gnomAD 11-14971168-AGGG-, CADD 17.00
- P8P (p.Pro8Pro), gnomAD 11-14971169-G-T, CADD 1.11
- P8A (p.Pro8Ala), gnomAD 11-14971171-G-C, REVEL 0.04, CADD 9.52
- F9C (p.Phe9Cys), gnomAD rs868931171
- F9L (p.Phe9Leu), ESP rs148481468, ExAC rs148481468, gnomAD rs148481468, REVEL 0.13, CADD 10.60
- F9Y (p.Phe9Tyr), gnomAD rs868931171, REVEL 0.32, CADD 23.70
- F9I (p.Phe9Ile), gnomAD 11-14971168-A-T, REVEL 0.17, CADD 19.70
- L10P (p.Leu10Pro), TOPMed rs1849594617
- A11T (p.Ala11Thr), rs1555026441, ClinGen CA379868633, ClinVar RCV004086272, gnomAD rs1555026441, REVEL 0.08, CADD 23.30, Uncertain significance, not specified
- A11V (p.Ala11Val), ExAC rs782689596, gnomAD rs782689596, REVEL 0.02, CADD 15.20
- A11A (p.Ala11Ala), gnomAD 11-14971160-A-T, CADD 12.50
- L12F (p.Leu12Phe), cosmic curated COSV10816
- L12I (p.Leu12Ile), cosmic curated COSV10963
- L12P (p.Leu12Pro), 1000Genomes rs200821703
- p.Leu12 Ser13insGluGlyGlyAlaGly, gnomAD 11-14971157-G-GCC, CADD 18.50
- L12S (p.Leu12Ser), gnomAD 11-14971158-AG-A, CADD 24.20
- S13N (p.Ser13Asn), gnomAD rs1555026435, REVEL 0.10, CADD 21.80
- S13R (p.Ser13Arg), gnomAD 11-14971154-G-C, REVEL 0.34, CADD 23.60
- I14R (p.Ile14Arg), gnomAD 11-14971148-CAAGA, CADD 28.10
- I14V (p.Ile14Val), gnomAD 11-14971153-T-C, REVEL 0.12, CADD 6.42
- L15F (p.Leu15Phe), 1000Genomes rs2133585831, REVEL 0.37, CADD 24.50
- L15L (p.Leu15Leu), gnomAD 11-14971148-C-T, CADD 11.70
- V16A (p.Val16Ala), TOPMed rs1272285854, REVEL 0.11, CADD 22.60
- V16I (p.Val16Ile), ExAC rs782409765, TOPMed rs782409765, gnomAD rs782409765, REVEL 0.03, CADD 17.10, Uncertain significance, not specified
- V16L (p.Val16Leu), ExAC rs782409765, TOPMed rs782409765, gnomAD rs782409765, REVEL 0.03, CADD 17.00
- V16V (p.Val16Val), rs1555026431, gnomAD 11-14971145-G-C, CADD 6.45
- L17P (p.Leu17Pro), ESP rs371778314, ExAC rs371778314, TOPMed rs371778314, gnomAD rs371778314, REVEL 0.27, CADD 26.50, Uncertain significance, not specified
- p.Leu17 Ser22delinsArg, rs781881425, gnomAD 11-14971128-CTGCC, CADD 19.20
- L17L (p.Leu17Leu), gnomAD 11-14971142-C-A, CADD 8.49
- L18M (p.Leu18Met), rs144571175, ClinGen CA5896988, ClinVar RCV004434489, ESP rs144571175, REVEL 0.05, CADD 18.10, Uncertain significance, not specified
- L18L (p.Leu18Leu), rs149287698, gnomAD 11-14971139-C-T, CADD 8.83
- Q19H (p.Gln19His), ExAC rs781820850, gnomAD rs781820850, REVEL 0.17, CADD 6.41
- A20T (p.Ala20Thr), gnomAD 11-14971135-C-T, REVEL 0.07, CADD 10.50
- G21D (p.Gly21Asp), gnomAD 11-14971131-C-T, REVEL 0.06, CADD 15.10
- S22R (p.Ser22Arg), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10052, REVEL 0.16, CADD 15.20, Variant assessed as somatic; moderate impact.
- L23L (p.Leu23Leu), rs139782606, gnomAD 11-14971124-G-C, CADD 2.13
- H24R (p.His24Arg), gnomAD rs1555026422
- H24H (p.His24His), rs201179955, gnomAD 11-14971121-A-G, CADD 0.29
- H24L (p.His24Leu), gnomAD 11-14971122-T-A, REVEL 0.10, CADD 22.30
- H24N (p.His24Asn), gnomAD 11-14971123-G-T, REVEL 0.04, CADD 18.20
- A25V (p.Ala25Val), TOPMed rs1555026419, gnomAD rs1555026419, REVEL 0.31, CADD 25.30
- A26E (p.Ala26Glu), TOPMed rs1258820939, gnomAD rs1258820939, REVEL 0.12, CADD 20.50
- A26A (p.Ala26Ala), rs781900545, gnomAD 11-14971115-T-C, CADD 0.59
- P27P (p.Pro27Pro), rs1555026414, gnomAD 11-14971112-T-A, CADD 4.26
- F28C (p.Phe28Cys), cosmic curated COSV59028
- R29S (p.Arg29Ser), 1000Genomes rs556800566, TOPMed rs556800566, REVEL 0.29, CADD 13.10
- R29K (p.Arg29Lys), gnomAD 11-14971107-C-T, REVEL 0.18, CADD 29.10
- S30C (p.Ser30Cys), ESP rs369544248, ExAC rs369544248, TOPMed rs369544248, gnomAD rs369544248, REVEL 0.16, CADD 22.00, Uncertain significance, not specified
- S30S (p.Ser30Ser), rs528241428, gnomAD 11-14970072-A-G, CADD 0.30
- S30A (p.Ser30Ala), gnomAD 11-14970074-A-C, REVEL 0.14, CADD 9.59
- A31P (p.Ala31Pro), 1000Genomes rs538582019, ExAC rs538582019, TOPMed rs538582019, gnomAD rs538582019, REVEL 0.12, CADD 10.90
- A31S (p.Ala31Ser), 1000Genomes rs538582019, ExAC rs538582019, TOPMed rs538582019, gnomAD rs538582019, REVEL 0.04, CADD 1.97, Uncertain significance, not specified
- A31T (p.Ala31Thr), 1000Genomes rs538582019, ExAC rs538582019, TOPMed rs538582019, gnomAD rs538582019, REVEL 0.05, CADD 4.67
- A31V (p.Ala31Val), TOPMed rs1555026185, gnomAD rs1555026185, REVEL 0.06, CADD 0.99
- A31A (p.Ala31Ala), gnomAD 11-14970069-G-C, CADD 2.00
- L32P (p.Leu32Pro), ExAC rs782307920, TOPMed rs782307920, gnomAD rs782307920, REVEL 0.22, CADD 22.20
- L32V (p.Leu32Val), 1000Genomes rs571272215, ExAC rs571272215, TOPMed rs571272215, gnomAD rs571272215, REVEL 0.16, CADD 8.59
- L32R (p.Leu32Arg), gnomAD 11-14970067-A-C, REVEL 0.26, CADD 17.00
- E33* (p.Glu33Ter), cosmic curated COSV10738
- E33G (p.Glu33Gly), ExAC rs782225521, gnomAD rs782225521, REVEL 0.14, CADD 19.60
- E33K (p.Glu33Lys), gnomAD rs1555026182, REVEL 0.26, CADD 23.00
- E33Q (p.Glu33Gln), gnomAD rs1555026182, REVEL 0.20, CADD 22.60
- E33D (p.Glu33Asp), gnomAD 11-14970063-C-G, REVEL 0.10, CADD 5.62
- S34S (p.Ser34Ser), rs1555026176, gnomAD 11-14970060-G-A, CADD 1.99
- S34N (p.Ser34Asn), gnomAD 11-14970061-C-T, REVEL 0.03, CADD 2.50
- S35G (p.Ser35Gly), cosmic curated COSV59028
- S35R (p.Ser35Arg), ExAC rs782503561, gnomAD rs782503561, REVEL 0.03, CADD 6.87
- S35T (p.Ser35Thr), cosmic curated COSV59028
- P36A (p.Pro36Ala), ExAC rs776680257, TOPMed rs776680257, gnomAD rs776680257, REVEL 0.11, CADD 14.40, Uncertain significance
- P36T (p.Pro36Thr), ExAC rs776680257, TOPMed rs776680257, gnomAD rs776680257, REVEL 0.07, CADD 15.30, Uncertain significance, not specified
- P36Q (p.Pro36Gln), gnomAD 11-14970054-TG-T, CADD 15.60
- P36P (p.Pro36Pro), gnomAD 11-14970054-T-G, CADD 2.26
- A37E (p.Ala37Glu), gnomAD rs1555026167, REVEL 0.04, CADD 1.13
- A37del (p.Ala37del), rs1555026165, gnomAD 11-14970049-TCTG-, CADD 4.26
- A37A (p.Ala37Ala), rs546905499, gnomAD 11-14970051-T-G, CADD 6.15
- D38A (p.Asp38Ala), Ensembl rs1849561833, REVEL 0.10, CADD 18.50
- D38E (p.Asp38Glu), TOPMed rs1849561731, REVEL 0.05, CADD 4.96
- D38G (p.Asp38Gly), gnomAD 11-14970049-T-TC, CADD 21.60
- D38N (p.Asp38Asn), gnomAD 11-14970050-C-T, REVEL 0.06, CADD 14.20
- P39L (p.Pro39Leu), cosmic curated COSV59028, ExAC rs782622457, gnomAD rs782622457, REVEL 0.07, CADD 0.14
- P39Q (p.Pro39Gln), ExAC rs782622457, gnomAD rs782622457, REVEL 0.10, CADD 0.54
- P39S (p.Pro39Ser), cosmic curated COSV59027
- P39P (p.Pro39Pro), rs1555026159, gnomAD 11-14970045-C-G, CADD 0.14
- A40V (p.Ala40Val), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10052, Variant assessed as somatic; moderate impact.
- A40A (p.Ala40Ala), gnomAD 11-14970042-G-C, CADD 3.19
- T41K (p.Thr41Lys), cosmic curated COSV59028
- T41M (p.Thr41Met), rs147263808, ClinGen CA218215924, ClinVar RCV004188690, ESP rs147263808, REVEL 0.07, CADD 9.21, Uncertain significance, not specified
- T41R (p.Thr41Arg), cosmic curated COSV59028
- T41T (p.Thr41Thr), rs143847934, gnomAD 11-14970039-C-G, CADD 0.21
- T41A (p.Thr41Ala), gnomAD 11-14970041-T-C, REVEL 0.03, CADD 2.15
- L42F (p.Leu42Phe), ExAC rs782336914, TOPMed rs782336914, gnomAD rs782336914, REVEL 0.22, CADD 23.30
- L42V (p.Leu42Val), ExAC rs782336914, TOPMed rs782336914, gnomAD rs782336914, REVEL 0.20, CADD 23.00
- L42L (p.Leu42Leu), gnomAD 11-14970036-G-A, CADD 5.78
- S43N (p.Ser43Asn), ExAC rs782220535, gnomAD rs782220535, REVEL 0.03, CADD 1.71
- S43G (p.Ser43Gly), gnomAD 11-14970035-T-C, REVEL 0.03, CADD 7.29
- E44V (p.Glu44Val), cosmic curated COSV59027
- E44E (p.Glu44Glu), rs1849560349, gnomAD 11-14970030-C-T, CADD 1.53
- E44* (p.Glu44Ter), gnomAD 11-14970032-C-A, CADD 35.00
- D45E (p.Asp45Glu), ESP rs138328117, ExAC rs138328117, TOPMed rs138328117, gnomAD rs138328117, REVEL 0.02, CADD 0.24, Likely benign, not specified
- D45G (p.Asp45Gly), ExAC rs782703642, gnomAD rs782703642, REVEL 0.04, CADD 21.70
- D45N (p.Asp45Asn), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10052, Variant assessed as somatic; moderate impact.
- D45Y (p.Asp45Tyr), rs1304418762, NCI-TCGA Cosmic COSV1005, TOPMed rs1304418762, gnomAD rs1304418762, REVEL 0.04, CADD 13.00, Variant assessed as somatic; moderate impact.
- D45D (p.Asp45Asp), rs138328117, gnomAD 11-14970027-G-A, CADD 2.10
- D45* (p.Asp45Ter), rs782589637, gnomAD 11-14970029-C-CA, CADD 21.80
- E46K (p.Glu46Lys), rs782339903, NCI-TCGA Cosmic COSV5902, cosmic curated COSV59027, ExAC rs782339903, REVEL 0.19, CADD 23.20, Variant assessed as somatic; moderate impact.
- E46S (p.Glu46Ser), rs782436578, gnomAD 11-14970026-C-CAC, CADD 22.80
- A47G (p.Ala47Gly), TOPMed rs1484959474, gnomAD rs1484959474
- A47T (p.Ala47Thr), ExAC rs782126509, REVEL 0.03, CADD 2.88
- A47V (p.Ala47Val), cosmic curated COSV59028, TOPMed rs1484959474, gnomAD rs1484959474, REVEL 0.05, CADD 5.18, Uncertain significance, not specified
- A47A (p.Ala47Ala), rs782043795, gnomAD 11-14970021-C-T, CADD 3.64
- A47E (p.Ala47Glu), gnomAD 11-14970022-G-T, REVEL 0.16, CADD 15.40
- A47P (p.Ala47Pro), gnomAD 11-14970023-C-G, REVEL 0.19, CADD 14.40
- A47R (p.Ala47Arg), rs781835072, gnomAD 11-14970023-CT-C, CADD 23.10
- R48C (p.Arg48Cys), cosmic curated COSV59027, ExAC rs782424054, TOPMed rs782424054, gnomAD rs782424054, REVEL 0.05, CADD 17.40
- R48H (p.Arg48His), ExAC rs782198733, TOPMed rs782198733, gnomAD rs782198733, REVEL 0.04, CADD 14.20
- R48L (p.Arg48Leu), cosmic curated COSV59027, REVEL 0.12, CADD 22.20
- R48P (p.Arg48Pro), rs1555026136, gnomAD 11-14970018-GC-G, CADD 21.00
- R48A (p.Arg48Ala), rs782728083, gnomAD 11-14970020-GC-G, CADD 12.30
- L49F (p.Leu49Phe), ExAC rs782583738, TOPMed rs782583738, gnomAD rs782583738, REVEL 0.05, CADD 23.80
- L49L (p.Leu49Leu), gnomAD 11-14970015-G-A, CADD 10.60
- L49P (p.Leu49Pro), gnomAD 11-14970016-A-G, REVEL 0.21, CADD 26.90
- L50M (p.Leu50Met), cosmic curated COSV10052
- L50P (p.Leu50Pro), cosmic curated COSV59027
- p.Leu50 Leu51insArgLysGlyIleTrpC, gnomAD 11-14970012-C-CCA, CADD 18.00
- L51L (p.Leu51Leu), gnomAD 11-14970011-G-A, CADD 10.70
- A52A (p.Ala52Ala), rs1555026129, gnomAD 11-14970006-A-T, CADD 9.24
- A53E (p.Ala53Glu), gnomAD rs1555026125, REVEL 0.22, CADD 19.90
- A53S (p.Ala53Ser), gnomAD rs1555026128, REVEL 0.16, CADD 13.70
- A53A (p.Ala53Ala), gnomAD 11-14970003-T-G, CADD 3.75
- L54L (p.Leu54Leu), gnomAD 11-14970000-C-T, CADD 9.88
- V55G (p.Val55Gly), Ensembl rs1590266397
- Q56H (p.Gln56His), gnomAD rs1849558168, REVEL 0.04, CADD 15.20
- Q56L (p.Gln56Leu), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10052, Variant assessed as somatic; moderate impact.
- Q56P (p.Gln56Pro), TOPMed rs1849558260, REVEL 0.13, CADD 23.40
- D57G (p.Asp57Gly), TOPMed rs1407551569, gnomAD rs1407551569, REVEL 0.10, CADD 25.00
- D57H (p.Asp57His), 1000Genomes rs5239, ESP rs5239, ExAC rs5239, TOPMed rs5239, CADD 23.60, PolyPhen-2 0.92
- D57N (p.Asp57Asn), rs5239, UniProt VAR 014592, UniProt VAR 048584, 1000Genomes rs5239, CADD 18.80, PolyPhen-2 0.08
- D57Y (p.Asp57Tyr), 1000Genomes rs5239, ESP rs5239, ExAC rs5239, TOPMed rs5239
- D57E (p.Asp57Glu), gnomAD 11-14969991-G-C, REVEL 0.04, CADD 18.00
- D57A (p.Asp57Ala), gnomAD 11-14969992-T-G, REVEL 0.09, CADD 20.20
- Y58C (p.Tyr58Cys), gnomAD rs1555026117
- Y58* (p.Tyr58Ter), gnomAD 11-14968937-G-T, CADD 38.00
- Y58S (p.Tyr58Ser), gnomAD 11-14968938-T-G, REVEL 0.34, CADD 27.30
- Y58H (p.Tyr58His), gnomAD 11-14968939-A-G, REVEL 0.34, CADD 27.60
- Y58Y (p.Tyr58Tyr), rs782216061, gnomAD 11-14969988-A-G, CADD 2.77
- V59A (p.Val59Ala), gnomAD rs1555026112, REVEL 0.10, CADD 21.00
- V59V (p.Val59Val), rs5240, gnomAD 11-14969985-C-A, CADD 9.35
- Q60H (p.Gln60His), ESP rs375799426, ExAC rs375799426, TOPMed rs375799426, gnomAD rs375799426, REVEL 0.27, CADD 23.60
- Q60Q (p.Gln60Gln), rs375799426, gnomAD 11-14969982-C-T, CADD 8.46
- Q60* (p.Gln60Ter), gnomAD 11-14969984-G-A, CADD 37.00
- M61I (p.Met61Ile), rs782463913, gnomAD 11-14968949-C-T, REVEL 0.07, CADD 22.20
- M61T (p.Met61Thr), gnomAD 11-14968950-A-G, REVEL 0.30, CADD 23.50
- M61L (p.Met61Leu), rs1237570565, gnomAD 11-14968951-T-G, REVEL 0.05, CADD 16.40
- K62K (p.Lys62Lys), rs1393396499, gnomAD 11-14969976-C-T, CADD 7.72
- A63D (p.Ala63Asp), cosmic curated COSV59027, ExAC rs782654358, TOPMed rs782654358, gnomAD rs782654358, REVEL 0.07, CADD 20.60
- A63S (p.Ala63Ser), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10052, Variant assessed as somatic; moderate impact.
- A63T (p.Ala63Thr), ExAC rs781905279, gnomAD rs781905279, REVEL 0.02, CADD 5.87
- S64N (p.Ser64Asn), NCI-TCGA Cosmic COSV1005, cosmic curated COSV10052, Variant assessed as somatic; moderate impact.
- S64T (p.Ser64Thr), gnomAD 11-14969971-C-G, REVEL 0.03, CADD 5.66
- E65D (p.Glu65Asp), TOPMed rs1333501130, gnomAD rs1333501130
Public CALCA analysis runs
- CALCA analysis run — CALCA (404 variants) — completed 2026-07-24