CASR (P41180) variants and mutations
CASR (also known as P41180) is a human protein-coding gene encoding an extracellular calcium-sensing receptor protein. It senses extracellular calcium in the parathyroid gland and kidney and adjusts parathyroid-hormone secretion and renal calcium handling accordingly. Loss-of-function variants cause familial hypocalciuric hypercalcemia or neonatal severe hyperparathyroidism, whereas activating variants cause autosomal dominant hypocalcemia. This analysis covers 2,483 CASR variants and mutations. Of these, 70% have computational variant effect predictions. Disease context includes familial hypocalciuric hypercalcemia 1, autosomal dominant hypocalcemia 1, and Familial hypocalciuric hypercalcemia type 1. Example CASR variants include M1L, M1R, and M1T.
Variant analysis overview
- Gene: CASR
- Protein: P41180
- UniProt accession: P41180
- Organism: Homo sapiens
- Variants analyzed: 2483
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 2,186 unspecified-consequence records; 201 synonymous variants; 77 missense variants; 11 frameshift variants; 2 in-frame deletions; 1 in-frame insertions; 1 splice-region variants; 4 stop-gained variants
- Prediction scores: 1,733 variants have prediction scores (70% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: familial hypocalciuric hypercalcemia 1, autosomal dominant hypocalcemia 1, Familial hypocalciuric hypercalcemia type 1, Familial isolated hypoparathyroidism, neonatal severe primary hyperparathyroidism, familial hypocalciuric hypercalcemia, autosomal dominant hypocalcemia, hyperparathyroidism, Hypercalcemia, parathyroid gland disorder, idiopathic generalized epilepsy, secondary hyperparathyroidism.
Protein structure and variant hotspots
- Protein features: 7 transmembrane segments; 22 binding sites; 16 post-translational modification sites.
- Structural context: 283 variants have structural context.
- PTM context: 32 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, MaveDB, LitVar.
Notable CASR variants
Examples include M1L, M1R, M1T, M1V, A2E, A2T, A2A, F3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs2107624704, ClinGen CA354361909, ClinVar RCV004061726, MetaLR 0.56, MetaSVM 0.10, Likely pathogenic, Nephrolithiasis/nephrocalcinosis
- M1R (p.Met1Arg), rs1467887809, ClinGen CA354361914, ClinVar RCV002651721, MetaLR 0.55, MetaSVM 0.22, Pathogenic, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- M1T (p.Met1Thr), rs1467887809, ClinGen CA354361913, ClinVar RCV002877444, ClinVar RCV003388129, MetaLR 0.55, MetaSVM 0.22, Pathogenic/Likely pathogenic, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- M1V (p.Met1Val), rs2107624704, ClinGen CA354361910, ClinVar RCV001779505, ClinVar RCV005213591, MetaLR 0.56, MetaSVM 0.10, Pathogenic/Likely pathogenic, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia; Familia
- A2E (p.Ala2Glu), cosmic curated COSV56138, Ensembl rs2074527714, CADD 14.50, PolyPhen-2 0.10
- A2T (p.Ala2Thr), NCI-TCGA Cosmic COSV9994, cosmic curated COSV99949, Uncertain significance, Nephrolithiasis/nephrocalcinosis
- A2A (p.Ala2Ala), rs112042188, gnomAD 3-122254195-A-C, CADD 3.65
- F3L (p.Phe3Leu), rs764556468, ClinGen CA354361930, ClinVar RCV001067696, Ensembl rs764556468, AlphaMissense 0.19, MetaLR 0.24, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- F3F (p.Phe3Phe), rs764556468, gnomAD 3-122254198-T-C, AlphaMissense 0.19, MetaLR 0.24
- Y4C (p.Tyr4Cys), rs1171102282, ClinGen CA354361936, ClinVar RCV000687843, ClinVar RCV000987309, CADD 18.10, PolyPhen-2 0.00, Uncertain significance, Nephrolithiasis/nephrocalcinosis; Autosomal dominant hypocalcemia 1; Familial hy
- Y4H (p.Tyr4His), rs1559955224, ClinGen CA354361932, ClinVar RCV002233448, ClinVar RCV004026752, AlphaMissense 0.09, MetaLR 0.45, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- Y4Y (p.Tyr4Tyr), rs1384647209, gnomAD 3-122254201-T-C, CADD 0.58
- S5G (p.Ser5Gly), gnomAD rs2074527950, CADD 3.83, PolyPhen-2 0.00
- S5R (p.Ser5Arg), rs2473204932, cosmic curated COSV56134, ClinGen CA354361946, ClinVar RCV004057413, CADD 14.90, PolyPhen-2 0.00, Uncertain significance, Nephrolithiasis/nephrocalcinosis
- S5T (p.Ser5Thr), gnomAD 3-122254203-G-C, CADD 16.70, PolyPhen-2 0.04
- S5S (p.Ser5Ser), gnomAD 3-122254204-C-T, CADD 9.39
- C6* (p.Cys6Ter), cosmic curated COSV56138
- C6G (p.Cys6Gly), rs1559955229, ClinGen CA354361950, ClinVar RCV002233190, ClinVar RCV004026329, CADD 17.80, PolyPhen-2 0.06, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- C6R (p.Cys6Arg), cosmic curated COSV56136
- C6S (p.Cys6Ser), gnomAD 3-122254205-T-A, CADD 16.50, PolyPhen-2 0.01
- C7F (p.Cys7Phe), rs2074528024, ClinGen CA354361961, ClinVar RCV001043770, Ensembl rs2074528024, CADD 12.40, PolyPhen-2 0.05, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- C7S (p.Cys7Ser), rs2074528024, ClinGen CA354361960, ClinVar RCV002023510, Ensembl rs2074528024, CADD 12.90, PolyPhen-2 0.06, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- C7W (p.Cys7Trp), rs1381043518, ClinGen CA354361963, ClinVar RCV004061209, gnomAD rs1381043518, CADD 17.00, PolyPhen-2 0.00, Uncertain significance, Nephrolithiasis/nephrocalcinosis
- C7Y (p.Cys7Tyr), rs2074528024, ClinGen CA354361959, ClinVar RCV001055733, ClinVar RCV005029625, CADD 8.71, PolyPhen-2 0.00, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Epileps
- V9D (p.Val9Asp), rs2473204987, ClinGen CA354361976, ClinVar RCV003806005, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- V9F (p.Val9Phe), rs2074528111, ClinGen CA354361975, cosmic curated COSV56137, ClinVar RCV002921996, CADD 14.90, PolyPhen-2 0.01, Uncertain significance, Nephrolithiasis/nephrocalcinosis; Autosomal dominant hypocalcemia 1; Familial hy
- V9I (p.Val9Ile), cosmic curated COSV56136, CADD 6.03, PolyPhen-2 0.00
- V9V (p.Val9Val), rs141880581, gnomAD 3-122254216-C-T, CADD 5.90
- L10F (p.Leu10Phe), rs1327682547, ClinGen CA354361981, ClinVar RCV001047886, ClinVar RCV004601342, CADD 14.00, PolyPhen-2 0.01, Uncertain significance, Nephrolithiasis/nephrocalcinosis; Autosomal dominant hypocalcemia 1; Familial hy
- L10I (p.Leu10Ile), rs1327682547, ClinGen CA354361979, NCI-TCGA Cosmic COSV5613, cosmic curated COSV56134, CADD 13.60, PolyPhen-2 0.03, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- L10V (p.Leu10Val), TOPMed rs1327682547, gnomAD rs1327682547, CADD 12.90, PolyPhen-2 0.01, Uncertain significance
- L11S (p.Leu11Ser), rs200673016, ClinGen CA2569405, ClinVar RCV000802402, ClinVar RCV001146802, CADD 23.20, PolyPhen-2 0.41, Conflicting interpretations, Autosomal dominant hypocalcemia 1; not provided; Nephrolithiasis/nephrocalcinosi
- L11F (p.Leu11Phe), gnomAD 3-122254222-G-T, CADD 17.10, PolyPhen-2 0.01
- A12G (p.Ala12Gly), cosmic curated COSV56142
- A12P (p.Ala12Pro), gnomAD 3-122254223-G-C, CADD 19.70, PolyPhen-2 0.39
- A12A (p.Ala12Ala), rs1262049687, gnomAD 3-122254225-A-G, CADD 0.33
- L13F (p.Leu13Phe), TOPMed rs201731619, CADD 9.62, PolyPhen-2 0.00
- L13P (p.Leu13Pro), rs104893717, ClinGen CA119539, ClinVar RCV000008858, ClinVar RCV004018601, AlphaMissense 0.13, MetaLR 0.50, Uncertain significance, Nephrolithiasis/nephrocalcinosis
- L13V (p.Leu13Val), TOPMed rs201731619
- L13L (p.Leu13Leu), gnomAD 3-122254228-C-T, CADD 0.20
- T14A (p.Thr14Ala), rs199515839, ClinGen CA2569406, ClinVar RCV000524604, ClinVar RCV001770431, CADD 0.64, PolyPhen-2 0.00, Conflicting interpretations, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- T14I (p.Thr14Ile), rs1235999733, ClinGen CA354362006, ClinVar RCV000705581, gnomAD rs1235999733, AlphaMissense 0.10, MetaLR 0.57, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- T14N (p.Thr14Asn), rs1235999733, ClinGen CA354362004, ClinVar RCV001339077, gnomAD rs1235999733, AlphaMissense 0.10, MetaLR 0.57, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- W15* (p.Trp15Ter), cosmic curated COSV56140, CADD 35.00
- W15G (p.Trp15Gly), rs2473205110, ClinGen CA354362008, ClinVar RCV003991523, ClinVar RCV004371922, Uncertain significance, Nephrolithiasis/nephrocalcinosis; Familial hypocalciuric hypercalcemia 1
- H16Y (p.His16Tyr), rs769932724, ClinGen CA2569407, ClinVar RCV002710526, ExAC rs769932724, CADD 0.01, PolyPhen-2 0.10, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- H16D (p.His16Asp), gnomAD 3-122254235-C-G, CADD 0.41, PolyPhen-2 0.00
- H16R (p.His16Arg), gnomAD 3-122254236-A-G, CADD 1.34, PolyPhen-2 0.04
- H16H (p.His16His), rs200520980, gnomAD 3-122254237-C-T, CADD 0.61
- T17I (p.Thr17Ile), rs1424489717, ClinGen CA354362028, ClinVar RCV000800988, ClinVar RCV004028045, CADD 2.77, PolyPhen-2 0.00, Uncertain significance, Nephrolithiasis/nephrocalcinosis; Epilepsy, idiopathic generalized, susceptibili
- T17P (p.Thr17Pro), cosmic curated COSV10810
- T17T (p.Thr17Thr), rs1483411909, gnomAD 3-122254240-C-T, CADD 1.42
- S18F (p.Ser18Phe), rs749748004, ClinGen CA2569409, ClinVar RCV002039460, ClinVar RCV002482429, CADD 22.20, PolyPhen-2 0.55, Uncertain significance, not specified; Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalc
- S18S (p.Ser18Ser), rs558522564, gnomAD 3-122254243-T-G, CADD 4.74
- A19P (p.Ala19Pro), rs2074528751, ClinGen CA354362035, ClinVar RCV001318159, Ensembl rs2074528751, CADD 22.70, PolyPhen-2 0.79, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- A19D (p.Ala19Asp), gnomAD 3-122254245-C-A, CADD 21.40, PolyPhen-2 0.37
- A19A (p.Ala19Ala), rs761576251, gnomAD 3-122254246-C-T, CADD 6.17
- Y20C (p.Tyr20Cys), rs2074528819, ClinGen CA354362044, ClinVar RCV004525651, TOPMed rs2074528819, CADD 24.50, PolyPhen-2 1.00, Uncertain significance, Nephrolithiasis/nephrocalcinosis
- Y20Y (p.Tyr20Tyr), rs201564143, gnomAD 3-122254249-C-T, CADD 0.39
- G21E (p.Gly21Glu), cosmic curated COSV10735
- G21R (p.Gly21Arg), rs1064794290, ClinGen CA16617810, NCI-TCGA Cosmic COSV5613, cosmic curated COSV56138, CADD 25.30, PolyPhen-2 1.00, Conflicting interpretations, Nephrolithiasis/nephrocalcinosis; Familial hypocalciuric hypercalcemia; Autosoma
- G21G (p.Gly21Gly), rs966820424, gnomAD 3-122254252-G-C, CADD 3.97
- P22L (p.Pro22Leu), NCI-TCGA Cosmic COSV5614, cosmic curated COSV56140, gnomAD rs2074529001, CADD 24.00, Variant assessed as somatic; moderate impact.
- P22S (p.Pro22Ser), rs2473205246, ClinGen CA354362054, ClinVar RCV004554912, Uncertain significance, CASR-related disorder
- P22P (p.Pro22Pro), gnomAD 3-122254255-A-T, CADD 1.09
- D23N (p.Asp23Asn), rs2107624826, ClinGen CA354362059, NCI-TCGA Cosmic COSV5614, cosmic curated COSV56140, AlphaMissense 0.07, MetaLR 0.33, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia; Nephrol
- Q24* (p.Gln24Ter), rs979596307, ClinGen CA354362068, ClinVar RCV003088759, AlphaMissense 0.10, MetaLR 0.57, Pathogenic
- Q24E (p.Gln24Glu), Ensembl rs979596307
- Q24L (p.Gln24Leu), NCI-TCGA Cosmic COSV9994, cosmic curated COSV99949, Variant assessed as somatic; moderate impact.
- Q24R (p.Gln24Arg), rs2473205278, ClinGen CA354362070, ClinVar RCV003786786, ClinVar RCV004366548, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia; Nephrol
- Q24Q (p.Gln24Gln), rs866536776, gnomAD 3-122254261-G-A, CADD 7.41
- R25* (p.Arg25Ter), rs201633414, ClinGen CA2569414, cosmic curated COSV56141, ClinVar RCV000413560, CADD 35.00, Pathogenic
- R25L (p.Arg25Leu), rs568902441, ClinGen CA82607490, cosmic curated COSV56138, ClinVar RCV001884705, CADD 24.60, PolyPhen-2 0.13, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- R25Q (p.Arg25Gln), rs568902441, ClinGen CA2569415, ClinVar RCV000531050, ClinVar RCV001755832, CADD 24.70, PolyPhen-2 0.94, Conflicting interpretations, Nephrolithiasis/nephrocalcinosis; Familial hypocalciuric hypercalcemia; Autosoma
- R25R (p.Arg25Arg), rs201633414, gnomAD 3-122254262-C-A, CADD 10.30
- A26V (p.Ala26Val), cosmic curated COSV56139
- A26A (p.Ala26Ala), rs77852524, gnomAD 3-122254267-C-A, CADD 9.63
- Q27P (p.Gln27Pro), gnomAD rs1451989725, CADD 26.00, PolyPhen-2 0.98
- Q27R (p.Gln27Arg), UniProt VAR 065198, Uncertain significance
- K28N (p.Lys28Asn), rs1290990935, ClinGen CA354362096, NCI-TCGA Cosmic COSV5613, cosmic curated COSV56136, CADD 25.40, PolyPhen-2 0.67, Uncertain significance, Nephrolithiasis/nephrocalcinosis
- K28Q (p.Lys28Gln), cosmic curated COSV56140
- K29E (p.Lys29Glu), rs397514729, ClinGen CA144613, ClinVar RCV000054483, Ensembl rs397514729, AlphaMissense 0.13, MetaLR 0.42, Pathogenic, Bartter syndrome with hypocalcemia
- G30E (p.Gly30Glu), rs1553765889, ClinGen CA354362108, NCI-TCGA Cosmic COSV5613, cosmic curated COSV56137, AlphaMissense 0.99, MetaLR 0.84, Uncertain significance, not specified; Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalc
- G30R (p.Gly30Arg), rs2074529480, ClinGen CA354362106, ClinVar RCV003801762, NCI-TCGA Cosmic COSV5613, CADD 28.10, PolyPhen-2 1.00, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- G30G (p.Gly30Gly), rs1055397172, gnomAD 3-122254279-G-A, CADD 8.72
- D31E (p.Asp31Glu), ExAC rs765124679, gnomAD rs765124679
- D31G (p.Asp31Gly), rs1064795924, ClinGen CA16617811, ClinVar RCV000478034, TOPMed rs1064795924, AlphaMissense 0.89, MetaLR 0.83, Uncertain significance, not provided
- D31H (p.Asp31His), rs2473205382, ClinGen CA354362111, ClinVar RCV003807050, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- D31N (p.Asp31Asn), NCI-TCGA Cosmic COSV5613, cosmic curated COSV56138, CADD 27.90, PolyPhen-2 0.80, Uncertain significance, Nephrolithiasis/nephrocalcinosis
- I32F (p.Ile32Phe), rs2074529687, ClinGen CA354362118, ClinVar RCV001341024, TOPMed rs2074529687, AlphaMissense 0.11, MetaLR 0.71, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- I32N (p.Ile32Asn), rs2473205402, ClinGen CA354362120, ClinVar RCV003490539, Uncertain significance, not provided
- I32V (p.Ile32Val), rs2074529687, ClinGen CA354362119, ClinVar RCV001986789, TOPMed rs2074529687, AlphaMissense 0.11, MetaLR 0.71, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- I32L (p.Ile32Leu), gnomAD 3-122254283-A-C, CADD 23.90, PolyPhen-2 0.28
- I32I (p.Ile32Ile), rs144604474, gnomAD 3-122254285-T-C, CADD 10.70
- I33S (p.Ile33Ser), rs758232331, ClinGen CA2569420, ClinVar RCV000819914, ClinVar RCV002487826, CADD 27.40, PolyPhen-2 0.46, Conflicting interpretations, Nephrolithiasis/nephrocalcinosis; Epilepsy, idiopathic generalized, susceptibili
- I33I (p.Ile33Ile), rs387907398, gnomAD 3-122254288-C-T, CADD 9.73
- L34F (p.Leu34Phe), cosmic curated COSV56135
- L34P (p.Leu34Pro), rs1559955362, ClinGen CA354362134, ClinVar RCV000711027, ClinVar RCV001231195, CADD 28.00, PolyPhen-2 1.00, Conflicting interpretations, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia; Neonata
- G35E (p.Gly35Glu), rs2473205445, ClinGen CA354362139, ClinVar RCV003040830, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- G35W (p.Gly35Trp), rs2473205437, ClinGen CA354362138, ClinVar RCV002303434, ClinVar RCV004047659, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- G35A (p.Gly35Ala), gnomAD 3-122254293-G-C, CADD 25.90, PolyPhen-2 0.87
- G35G (p.Gly35Gly), rs2107624919, gnomAD 3-122254294-G-A, CADD 6.04
- G36R (p.Gly36Arg), rs193922420, ClinGen CA213559, ClinVar RCV000341520, ClinVar RCV000705981, CADD 28.00, PolyPhen-2 1.00, Conflicting interpretations, Nephrolithiasis/nephrocalcinosis; Familial hyperparathyroidism or Hypocalciuric
- G36V (p.Gly36Val), rs1559955372, ClinGen CA354362146, cosmic curated COSV56134, ClinVar RCV002233725, AlphaMissense 0.99, MetaLR 0.82, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; not spe
- G36G (p.Gly36Gly), rs781573002, gnomAD 3-122254297-G-A, CADD 4.09
- L37F (p.Leu37Phe), rs2473205478, ClinGen CA354362147, ClinVar RCV004525558, ClinVar RCV006454534, Uncertain significance, Nephrolithiasis/nephrocalcinosis; not specified
- L37P (p.Leu37Pro), rs2473205484, ClinGen CA354362151, ClinVar RCV003781009, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- L37A (p.Leu37Ala), rs886041823, gnomAD 3-122254291-T-TG, CADD 32.00
- L37S (p.Leu37Ser), rs886041823, gnomAD 3-122254291-TG-T, CADD 29.00
- F38L (p.Phe38Leu), rs61733590, ClinGen CA354362159, ClinVar RCV003804169, CADD 27.80, PolyPhen-2 1.00, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- F38F (p.Phe38Phe), rs61733590, gnomAD 3-122254303-T-C, CADD 11.30
- P39A (p.Pro39Ala), rs121909262, ClinGen CA119499, ClinVar RCV000008832, UniProt VAR 003585, AlphaMissense 0.94, MetaLR 0.79, Pathogenic, Familial hypocalciuric hypercalcemia 1
- P39S (p.Pro39Ser), rs121909262, ClinGen CA82607564, NCI-TCGA Cosmic COSV5613, cosmic curated COSV56133, AlphaMissense 0.94, MetaLR 0.79, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- P39T (p.Pro39Thr), cosmic curated COSV10460
- P39P (p.Pro39Pro), rs1316125812, gnomAD 3-122254306-T-G, CADD 10.90
- I40V (p.Ile40Val), rs1458833527, ClinGen CA354362166, ClinVar RCV001062218, ClinVar RCV002489676, CADD 19.40, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia; Epileps
- H41N (p.His41Asn), rs2473205535, ClinGen CA354362174, ClinVar RCV002302092, ClinVar RCV003984249, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- H41R (p.His41Arg), gnomAD 3-122254311-A-G, CADD 25.40, PolyPhen-2 1.00
- H41H (p.His41His), rs1331565057, gnomAD 3-122254312-T-C, CADD 11.20
- F42S (p.Phe42Ser), rs1553765909, ClinGen CA354362184, ClinVar RCV002232605, ClinVar RCV006552573, AlphaMissense 0.80, MetaLR 0.66, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; not pro
- G43E (p.Gly43Glu), NCI-TCGA Cosmic COSV5613, cosmic curated COSV56136, Variant assessed as somatic; moderate impact.
- G43R (p.Gly43Arg), rs866899753, ClinGen CA82607569, ClinVar RCV001319156, ClinVar RCV005023031, AlphaMissense 0.88, MetaLR 0.75, Uncertain significance, Familial hypocalciuric hypercalcemia 1; Autosomal dominant hypocalcemia 1; Neona
- G43A (p.Gly43Ala), gnomAD 3-122254317-G-C, CADD 23.40, PolyPhen-2 0.95
- G43G (p.Gly43Gly), rs756322119, gnomAD 3-122254318-A-G, CADD 14.60
- V44E (p.Val44Glu), rs2074530498, ClinGen CA354362196, ClinVar RCV001913027, ClinVar RCV004041791, CADD 25.10, PolyPhen-2 0.96, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- V44I (p.Val44Ile), rs2074530467, ClinGen CA354362193, ClinVar RCV001360501, ClinVar RCV002486509, CADD 21.60, PolyPhen-2 0.07, Uncertain significance, Nephrolithiasis/nephrocalcinosis; Familial hypocalciuric hypercalcemia; Autosoma
- V44V (p.Val44Val), gnomAD 3-122254321-A-T, CADD 10.20
- A45E (p.Ala45Glu), rs779995504, ClinGen CA2569424, ClinVar RCV000472590, ClinVar RCV001764431, AlphaMissense 0.21, MetaLR 0.56, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia; Nephrol
- A45G (p.Ala45Gly), ExAC rs779995504, gnomAD rs779995504, AlphaMissense 0.21, MetaLR 0.56, Uncertain significance
- A45T (p.Ala45Thr), Ensembl rs1576852270
- A45V (p.Ala45Val), rs779995504, ClinGen CA354362202, ClinVar RCV001222412, ExAC rs779995504, AlphaMissense 0.21, MetaLR 0.56, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- A46T (p.Ala46Thr), gnomAD rs1329833347, CADD 21.20, PolyPhen-2 0.37
- K47E (p.Lys47Glu), rs2107624989, ClinGen CA354362210, ClinVar RCV002249328, Ensembl rs2107624989, AlphaMissense 0.27, MetaLR 0.61, Pathogenic, Familial hypocalciuric hypercalcemia 1
- K47N (p.Lys47Asn), rs104893702, ClinGen CA119511, ClinVar RCV000008839, UniProt VAR 058050, AlphaMissense 0.64, MetaLR 0.64, Pathogenic, Autosomal dominant hypocalcemia 1
- K47R (p.Lys47Arg), gnomAD 3-122254329-A-G, CADD 24.50, PolyPhen-2 0.22
- D48N (p.Asp48Asn), rs2473205661, ClinGen CA354362216, ClinVar RCV003812526, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- D48D (p.Asp48Asp), gnomAD 3-122254333-T-C, CADD 11.70
- Q49* (p.Gln49Ter), cosmic curated COSV10810
- Q49E (p.Gln49Glu), rs1553765913, ClinGen CA354362225, ClinVar RCV000639432, ClinVar RCV004025545, AlphaMissense 0.08, MetaLR 0.40, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- Q49R (p.Gln49Arg), rs1212959682, ClinGen CA354362228, ClinVar RCV004058002, gnomAD rs1212959682, CADD 22.40, PolyPhen-2 0.46, Uncertain significance, Nephrolithiasis/nephrocalcinosis
- Q49Q (p.Gln49Gln), rs2074530803, gnomAD 3-122254336-A-G, CADD 10.10
- D50G (p.Asp50Gly), rs1174370617, ClinGen CA354362236, ClinVar RCV001896880, TOPMed rs1174370617, AlphaMissense 0.39, MetaLR 0.68, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- D50V (p.Asp50Val), rs1174370617, ClinGen CA354362237, ClinVar RCV001243613, ClinVar RCV004034755, AlphaMissense 0.39, MetaLR 0.68, Uncertain significance, Nephrolithiasis/nephrocalcinosis; Familial hypocalciuric hypercalcemia; Autosoma
- D50D (p.Asp50Asp), rs769021483, gnomAD 3-122254339-T-C, CADD 10.80
- L51F (p.Leu51Phe), rs996249687, ClinGen CA82607604, ClinVar RCV001228902, ClinVar RCV004032653, CADD 22.30, PolyPhen-2 1.00, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia; Nephrol
- L51I (p.Leu51Ile), cosmic curated COSV10941
- K52E (p.Lys52Glu), rs2473205722, ClinGen CA354362246, ClinVar RCV002303288, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- K52I (p.Lys52Ile), rs1553765922, ClinGen CA354362250, ClinVar RCV003774384, ClinVar RCV004059115, AlphaMissense 0.08, MetaLR 0.42, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- K52R (p.Lys52Arg), rs1553765922, ClinGen CA354362249, ClinVar RCV002232611, Ensembl rs1553765922, AlphaMissense 0.08, MetaLR 0.42, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- K52Q (p.Lys52Gln), gnomAD 3-122254343-A-C, CADD 18.40, PolyPhen-2 0.13
- S53* (p.Ser53Ter), rs2473205737, ClinGen CA354362257, ClinVar RCV003994927, Pathogenic, in HHC1
- S53L (p.Ser53Leu), cosmic curated COSV56139, CADD 23.10, PolyPhen-2 0.28
- S53P (p.Ser53Pro), rs2107625030, ClinGen CA354362254, ClinVar RCV002238566, ClinVar RCV006558661, AlphaMissense 0.78, MetaLR 0.65, Pathogenic, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- S53S (p.Ser53Ser), gnomAD 3-122254348-A-C, CADD 11.50
- R54S (p.Arg54Ser), rs2074531100, ClinGen CA354362264, ClinVar RCV001342401, Ensembl rs2074531100, AlphaMissense 0.90, MetaLR 0.67, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1
- R54R (p.Arg54Arg), rs2074531057, gnomAD 3-122254349-A-C, CADD 13.00
- P55L (p.Pro55Leu), rs886041154, ClinGen CA10602861, ClinVar RCV000401051, ClinVar RCV000815977, CADD 26.30, PolyPhen-2 1.00, Pathogenic, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- P55S (p.Pro55Ser), rs2107625041, ClinGen CA354362268, ClinVar RCV003052285, NCI-TCGA TCGA novel, AlphaMissense 0.95, MetaLR 0.84, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- P55T (p.Pro55Thr), Ensembl rs2107625041
- P55P (p.Pro55Pro), rs200018529, gnomAD 3-122254354-G-A, CADD 3.02
- E56* (p.Glu56Ter), rs1358793834, ClinGen CA354362273, ClinVar RCV001039545, ClinVar RCV001536112, CADD 39.00, Pathogenic
- E56D (p.Glu56Asp), gnomAD rs1250155407, CADD 23.00, PolyPhen-2 0.93
- E56V (p.Glu56Val), rs2107625061, ClinGen CA354362275, ClinVar RCV001935908, Ensembl rs2107625061, AlphaMissense 0.32, MetaLR 0.75, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- S57S (p.Ser57Ser), rs1417542131, gnomAD 3-122254360-T-C, CADD 2.94
- V58E (p.Val58Glu), rs2107625078, ClinGen CA354362290, ClinVar RCV001779506, Ensembl rs2107625078, AlphaMissense 0.29, MetaLR 0.51, Uncertain significance, not specified
- V58L (p.Val58Leu), rs1161795745, cosmic curated COSV99948, ClinGen CA354362286, ClinVar RCV001054997, CADD 19.30, PolyPhen-2 0.00, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; Nephrol
- V58M (p.Val58Met), gnomAD 3-122254361-G-A, CADD 22.60, PolyPhen-2 0.57
- E59G (p.Glu59Gly), rs2473205852, ClinGen CA354362295, ClinVar RCV003100823, ClinVar RCV004061383, CADD 23.40, PolyPhen-2 0.64, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia; Nephrol
- E59K (p.Glu59Lys), rs2107625081, ClinGen CA354362291, ClinVar RCV001903693, ClinVar RCV006453797, AlphaMissense 0.14, MetaLR 0.38, Uncertain significance, Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1; not spe
- E59E (p.Glu59Glu), rs200756928, gnomAD 3-122254366-A-G, CADD 10.30
- C60F (p.Cys60Phe), rs772906030, ClinGen CA354362303, ClinVar RCV002233556, ClinVar RCV002473113, CADD 28.80, PolyPhen-2 1.00, Uncertain significance, not provided; Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalce
- C60R (p.Cys60Arg), rs2473205862, ClinGen CA354362300, ClinVar RCV004554898, Uncertain significance, CASR-related disorder
- C60Y (p.Cys60Tyr), cosmic curated COSV10516, ExAC rs772906030, TOPMed rs772906030, gnomAD rs772906030, CADD 28.50, PolyPhen-2 1.00, Uncertain significance
- C60C (p.Cys60Cys), gnomAD 3-122254369-T-C, CADD 10.80
- I61L (p.Ile61Leu), rs2074531605, ClinGen CA354362306, ClinVar RCV001315221, Ensembl rs2074531605, AlphaMissense 0.14, MetaLR 0.42, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- I61T (p.Ile61Thr), TOPMed rs2074531640
- I61V (p.Ile61Val), rs2074531605, ClinGen CA354362307, ClinVar RCV004059369, AlphaMissense 0.14, MetaLR 0.42, Uncertain significance, Nephrolithiasis/nephrocalcinosis
- R62G (p.Arg62Gly), cosmic curated COSV56141
- R62K (p.Arg62Lys), rs121909265, ClinGen CA354362315, ClinVar RCV003801608, AlphaMissense 0.85, MetaLR 0.83, Uncertain significance, Autosomal dominant hypocalcemia 1; Familial hypocalciuric hypercalcemia
- R62M (p.Arg62Met), rs121909265, ClinGen CA119505, ClinVar RCV000008836, UniProt VAR 003586, AlphaMissense 0.85, MetaLR 0.83, Pathogenic, Familial hypocalciuric hypercalcemia 1
Public CASR analysis runs
- CASR analysis run — CASR (2,483 variants) — completed 2026-08-21