LDLR (Low-density lipoprotein receptor) variants and mutations
LDLR (also known as Low-density lipoprotein receptor) is a human protein-coding gene encoding a low-density lipoprotein receptor protein. It removes ApoB-containing LDL particles from the circulation through receptor-mediated endocytosis, especially in hepatocytes. Loss-of-function variants are the most common cause of familial hypercholesterolemia and lead to lifelong LDL elevation and premature atherosclerotic disease. This analysis covers 2,294 LDLR variants and mutations. Of these, 87% have computational variant effect predictions. Disease context includes hypercholesterolemia, familial, 1, Hypercholesterolemia, and familial hypercholesterolemia. Example LDLR variants include M1I, M1L, and M1T.
Variant analysis overview
- Gene: LDLR
- Protein: Low-density lipoprotein receptor
- UniProt accession: P01130
- Organism: Homo sapiens
- Variants analyzed: 2294
- Variant scope: all variants
- Completed: 2026-08-10
Variant and mutation evidence
- Variant composition: 2,101 unspecified-consequence records; 57 synonymous variants; 109 missense variants; 13 frameshift variants; 3 in-frame deletions; 1 coding sequence variant; 2 stop-gained variants; 1 in-frame insertions; 2 splice-region variants; 5 substitution
- Prediction scores: 1,998 variants have prediction scores (87% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypercholesterolemia, familial, 1, Hypercholesterolemia, familial hypercholesterolemia, homozygous familial hypercholesterolemia, coronary artery disorder, metabolic disease, heart disorder, hyperlipidemia, angina pectoris, Disorder of lipid metabolism, metabolic syndrome, myocardial infarction.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 10 domains; 6 post-translational modification sites.
- Structural context: 1,282 variants have structural context.
- PTM context: 8 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 LDLR variants
Examples include M1I, M1L, M1T, M1V, G2E, G2R, G2G, G2W. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs879254383, ClinGen CA404071097, ClinVar RCV000508870, ClinGen CA10584721, MetaLR 0.76, MetaSVM 0.62, Likely pathogenic, Hypercholesterolemia, familial, 1
- M1L (p.Met1Leu), rs879254382, ClinGen CA10584720, ClinVar RCV000238419, ClinVar RCV001220717, MetaLR 0.73, MetaSVM 0.54, Pathogenic, Hypercholesterolemia, familial, 1
- M1T (p.Met1Thr), rs1555800701, ClinGen CA404071092, ClinVar RCV000509477, ClinVar RCV000588649, MetaLR 0.77, MetaSVM 0.63, Likely pathogenic, Hypercholesterolemia, familial, 1
- M1V (p.Met1Val), rs879254382, ClinGen CA10584719, ClinVar RCV000237949, ClinVar RCV002418050, MetaLR 0.73, MetaSVM 0.54, Likely pathogenic, Hypercholesterolemia, familial, 1
- G2E (p.Gly2Glu), TOPMed rs1426542050, gnomAD rs1426542050, CADD 9.65
- G2R (p.Gly2Arg), rs5931, ClinGen CA085719, cosmic curated COSV52943, ClinVar RCV000237142, CADD 11.70, PolyPhen-2 0.00, Uncertain significance, Hypercholesterolemia, familial, 1
- G2G (p.Gly2Gly), gnomAD 19-11089554-G-T, CADD 3.76
- G2W (p.Gly2Trp), gnomAD 19-11090601-G-T, CADD 4.95, SIFT 0.00
- P3T (p.Pro3Thr), rs2077057129, ClinGen CA404071196, ClinVar RCV004015882, Ensembl rs2077057129, CADD 3.53, PolyPhen-2 0.04, Uncertain significance, Hypercholesterolemia, familial, 1
- P3L (p.Pro3Leu), gnomAD 19-11089556-C-T, CADD 14.40, PolyPhen-2 0.08
- P3P (p.Pro3Pro), rs2147186453, gnomAD 19-11089557-C-T, CADD 3.27
- P3S (p.Pro3Ser), rs1048561668, gnomAD 19-11090607-C-T, CADD 6.74, SIFT 0.00
- P3R (p.Pro3Arg), rs1259779740, gnomAD 19-11090608-C-G, CADD 4.16, SIFT 0.00
- P3H (p.Pro3His), rs1259779740, gnomAD 19-11090608-C-A, CADD 3.96, SIFT 0.00
- P3Q (p.Pro3Gln), gnomAD 19-11090620-C-A, CADD 0.58, SIFT 0.00
- P3A (p.Pro3Ala), rs748476021, gnomAD 19-11090658-C-G, CADD 5.06, SIFT 0.00
- W4* (p.Trp4Ter), rs201016593, ClinGen CA10584724, ClinVar RCV000237276, ClinVar RCV001221497, CADD 31.00, Pathogenic
- W4C (p.Trp4Cys), gnomAD 19-11089560-G-C, CADD 5.45, PolyPhen-2 0.19
- G5D (p.Gly5Asp), TOPMed rs989812477, CADD 2.13
- G5C (p.Gly5Cys), rs1474228297, gnomAD 19-11090610-G-T, CADD 0.13, SIFT 0.00
- G5R (p.Gly5Arg), rs1474228297, gnomAD 19-11090610-G-C, CADD 0.14, SIFT 0.00
- G5S (p.Gly5Ser), gnomAD 19-11090610-G-A, CADD 0.17, SIFT 0.00
- G5G (p.Gly5Gly), gnomAD 19-11090612-C-T, CADD 0.40
- W6* (p.Trp6Ter), rs2515907266, ClinGen CA404071328, ClinVar RCV004018066, NCI-TCGA TCGA novel, CADD 33.00, Likely pathogenic
- W6F (p.Trp6Phe), rs774615547, gnomAD 19-11089562-G-GCT, CADD 22.50
- K7N (p.Lys7Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K7K (p.Lys7Lys), rs2147186490, gnomAD 19-11089569-A-G, CADD 4.55
- L8* (p.Leu8Ter), rs2515907293, ClinGen CA404071404, ClinVar RCV004280081, ClinVar RCV006634834, Pathogenic
- R9H (p.Arg9His), TOPMed rs1004937473, CADD 22.80, PolyPhen-2 0.78
- R9P (p.Arg9Pro), TOPMed rs1004937473, Uncertain significance, Cardiovascular phenotype
- R9S (p.Arg9Ser), gnomAD 19-11089573-C-A, CADD 9.72, PolyPhen-2 0.05
- R9R (p.Arg9Arg), gnomAD 19-11089575-C-A, CADD 12.70
- R9W (p.Arg9Trp), rs2077074813, gnomAD 19-11090604-A-T, CADD 7.00, SIFT 0.00
- R9G (p.Arg9Gly), gnomAD 19-11090604-A-G, CADD 7.43, SIFT 0.00
- R9M (p.Arg9Met), rs899991550, gnomAD 19-11090605-G-T, CADD 0.84, SIFT 0.00
- R9K (p.Arg9Lys), rs1305381653, gnomAD 19-11090638-G-A, CADD 6.18, SIFT 0.00
- R16del (p.Arg16del), rs1384060147, gnomAD 19-11090639-GCGA-, CADD 7.03
- R9* (p.Arg9Ter), gnomAD 19-11090643-C-T, CADD 6.99
- R9L (p.Arg9Leu), rs758004591, gnomAD 19-11090644-G-T, CADD 0.60, SIFT 0.00
- R9Q (p.Arg9Gln), gnomAD 19-11090644-G-A, CADD 0.74, SIFT 0.00
- W10* (p.Trp10Ter), rs1568582652, ClinGen CA404071509, ClinVar RCV000771735, ClinVar RCV004017730, Pathogenic
- W10R (p.Trp10Arg), rs879254386, ClinGen CA10584725, ClinVar RCV000237216, Ensembl rs879254386, AlphaMissense 0.55, MetaLR 0.59, Pathogenic/Likely pathogenic, Cardiovascular phenotype; Familial hypercholesterolemia; Hypercholesterolemia, f
- W10G (p.Trp10Gly), gnomAD 19-11089574-GC-G, CADD 24.40
- W10C (p.Trp10Cys), gnomAD 19-11089578-G-T, CADD 22.60, PolyPhen-2 0.01
- T11I (p.Thr11Ile), ExAC rs777266061, gnomAD rs777266061, CADD 5.04, PolyPhen-2 0.00
- T11S (p.Thr11Ser), rs1600683674, ClinGen CA404071528, ClinVar RCV000797028, Ensembl rs1600683674, AlphaMissense 0.11, MetaLR 0.45, Uncertain significance, Familial hypercholesterolemia
- T11A (p.Thr11Ala), gnomAD 19-11089579-A-G, CADD 10.70, PolyPhen-2 0.00
- T11T (p.Thr11Thr), rs748734643, gnomAD 19-11089581-C-G, CADD 6.91
- V12I (p.Val12Ile), gnomAD rs1470135357, CADD 1.56, PolyPhen-2 0.00
- V12L (p.Val12Leu), gnomAD 19-11089582-G-C, CADD 2.92, PolyPhen-2 0.01
- V12V (p.Val12Val), gnomAD 19-11089584-C-A, CADD 8.07
- V12F (p.Val12Phe), rs1004149250, gnomAD 19-11090613-G-T, CADD 7.96, SIFT 0.00
- V12A (p.Val12Ala), gnomAD 19-11090614-T-C, CADD 8.38, SIFT 0.00
- A13T (p.Ala13Thr), TOPMed rs2077057718
- A13V (p.Ala13Val), gnomAD rs2077057804, CADD 11.80, PolyPhen-2 0.15
- p.Ala13 Ala19del, rs1469062460, gnomAD 19-11089584-CGCCT, CADD 19.40
- L14* (p.Leu14Ter), rs1600683731, ClinGen CA404071622, ClinVar RCV000822108, ClinVar RCV005589904, Pathogenic
- L14F (p.Leu14Phe), rs369608025, ClinGen CA085656, ClinVar RCV001188426, ESP rs369608025, CADD 15.90, PolyPhen-2 0.01, Uncertain significance, Familial hypercholesterolemia
- L14L (p.Leu14Leu), gnomAD 19-11089590-G-A, CADD 8.37
- L15F (p.Leu15Phe), TOPMed rs2077057972, CADD 13.90, PolyPhen-2 0.01, Uncertain significance, Familial hypercholesterolemia
- L15H (p.Leu15His), rs879254390, ClinGen CA10584731, ClinVar RCV000238308, Ensembl rs879254390, AlphaMissense 0.38, MetaLR 0.79, Uncertain significance, Hypercholesterolemia, familial, 1
- L15P (p.Leu15Pro), rs879254390, ClinGen CA10584732, ClinVar RCV000237294, ClinVar RCV001062304, AlphaMissense 0.38, MetaLR 0.79, Likely pathogenic, Hypercholesterolemia, familial, 1
- L15R (p.Leu15Arg), rs879254390, ClinGen CA404071695, ClinVar RCV001946479, Ensembl rs879254390, AlphaMissense 0.38, MetaLR 0.79, Likely pathogenic, Familial hypercholesterolemia
- L15L (p.Leu15Leu), rs778389514, gnomAD 19-11089593-C-T, CADD 4.29
- L16P (p.Leu16Pro), rs879254391, ClinGen CA10584733, ClinVar RCV000237870, Ensembl rs879254391, AlphaMissense 0.38, MetaLR 0.72, Uncertain significance, Hypercholesterolemia, familial, 1
- L16V (p.Leu16Val), rs2077058105, ClinGen CA404071705, ClinVar RCV001177803, ClinVar RCV002505759, CADD 9.15, PolyPhen-2 0.07, Uncertain significance, Hypercholesterolemia, familial, 1
- L16F (p.Leu16Phe), gnomAD 19-11089594-C-T, CADD 10.10, PolyPhen-2 0.01
- L16I (p.Leu16Ile), gnomAD 19-11089594-C-A, CADD 8.93, PolyPhen-2 0.01
- L16L (p.Leu16Leu), rs565675103, gnomAD 19-11089596-C-A, CADD 6.11
- L16M (p.Leu16Met), gnomAD 19-11090703-C-A, CADD 4.52, SIFT 0.00
- A17P (p.Ala17Pro), TOPMed rs1201172788, gnomAD rs1201172788
- A17S (p.Ala17Ser), TOPMed rs1201172788, gnomAD rs1201172788, CADD 6.58, PolyPhen-2 0.01
- A17T (p.Ala17Thr), rs1201172788, ClinGen CA404071735, ClinVar RCV004013115, ClinVar RCV006550989, CADD 10.40, PolyPhen-2 0.10, Conflicting interpretations, Familial hypercholesterolemia; Hypercholesterolemia, familial, 1
- A17A (p.Ala17Ala), rs2077058281, gnomAD 19-11089599-C-T, CADD 4.37
- A18P (p.Ala18Pro), rs1172805138, ClinGen CA404071765, ClinVar RCV002247944, gnomAD rs1172805138, AlphaMissense 0.16, MetaLR 0.55, Uncertain significance, not specified
- A18T (p.Ala18Thr), gnomAD rs1172805138, Uncertain significance
- A18V (p.Ala18Val), rs1057519651, ClinGen CA16602290, ClinVar RCV000417268, Ensembl rs1057519651, AlphaMissense 0.15, MetaLR 0.50, Likely benign, Hypercholesterolemia, familial, 1
- A18S (p.Ala18Ser), gnomAD 19-11089600-G-T, CADD 15.90, PolyPhen-2 0.40
- A18A (p.Ala18Ala), gnomAD 19-11089602-G-A, CADD 1.85
- A19E (p.Ala19Glu), rs879254392, ClinGen CA10584734, ClinVar RCV000237342, ClinVar RCV005890972, AlphaMissense 0.15, MetaLR 0.47, Uncertain significance, not specified; Hypercholesterolemia, familial, 1
- A19G (p.Ala19Gly), rs879254392, ClinGen CA404071816, ClinVar RCV001524830, ClinVar RCV004808083, AlphaMissense 0.15, MetaLR 0.47, Uncertain significance, Familial hypercholesterolemia; Hypercholesterolemia, familial, 1
- A19P (p.Ala19Pro), NCI-TCGA Cosmic COSV9936, cosmic curated COSV99369, Variant assessed as somatic; moderate impact.
- A19V (p.Ala19Val), rs879254392, ClinGen CA10584735, ClinVar RCV000237997, ClinVar RCV001182217, AlphaMissense 0.15, MetaLR 0.47, Conflicting interpretations, Familial hypercholesterolemia; not provided; Hypercholesterolemia, familial, 1
- A19T (p.Ala19Thr), gnomAD 19-11089603-G-A, CADD 12.40, PolyPhen-2 0.00
- A19A (p.Ala19Ala), gnomAD 19-11089605-G-T, CADD 3.84
- G20E (p.Gly20Glu), rs1568582750, ClinGen CA404071849, ClinVar RCV000777546, ClinVar RCV002227216, CADD 7.32, PolyPhen-2 0.00, Uncertain significance, Hypercholesterolemia, familial, 1
- G20R (p.Gly20Arg), rs147509697, ClinGen CA023728, ClinVar RCV000161949, ClinVar RCV000211611, CADD 14.60, PolyPhen-2 0.10, Benign, Hypercholesterolemia, familial, 1
- G20W (p.Gly20Trp), gnomAD 19-11089606-G-T, CADD 20.60, PolyPhen-2 0.37
- G20A (p.Gly20Ala), gnomAD 19-11089607-G-C, CADD 6.08, PolyPhen-2 0.00
- G20G (p.Gly20Gly), gnomAD 19-11089608-G-C, CADD 7.09
- G20C (p.Gly20Cys), gnomAD 19-11090655-G-T, CADD 7.24, SIFT 0.00
- T21P (p.Thr21Pro), Ensembl rs2147186706, CADD 9.45, PolyPhen-2 0.02
- T21T (p.Thr21Thr), rs1475090608, gnomAD 19-11089611-T-G, CADD 10.10
- A22S (p.Ala22Ser), rs942568624, ClinGen CA305287461, ClinVar RCV000775622, ClinVar RCV004001460, CADD 16.60, PolyPhen-2 0.01, Uncertain significance, Hypercholesterolemia, familial, 1; Familial hypercholesterolemia
- A22V (p.Ala22Val), ExAC rs777132399, gnomAD rs777132399, CADD 22.70, PolyPhen-2 0.18, Uncertain significance, Familial hypercholesterolemia
- V23M (p.Val23Met), TOPMed rs1704517900, CADD 33.00, PolyPhen-2 0.54
- V23I (p.Val23Ile), rs1210310746, gnomAD 19-11090649-G-A, CADD 3.58, SIFT 0.00
- V23L (p.Val23Leu), rs1210310746, gnomAD 19-11090649-G-C, CADD 3.16, SIFT 0.00
- V23V (p.Val23Val), gnomAD 19-11090651-C-A, CADD 9.32
- G24S (p.Gly24Ser), gnomAD rs1767610199, CADD 12.30, PolyPhen-2 0.06
- G24V (p.Gly24Val), rs1442411392, gnomAD rs1442411392, CADD 5.91, PolyPhen-2 0.01, Variant assessed as somatic; moderate impact.
- G24A (p.Gly24Ala), gnomAD 19-11100223-TG-T, CADD 13.40
- G24D (p.Gly24Asp), gnomAD 19-11100226-G-A, MetaLR 0.46, MetaSVM -0.45
- G24G (p.Gly24Gly), gnomAD 19-11100227-C-G, CADD 5.05
- D25H (p.Asp25His), 1000Genomes rs562712652, ExAC rs562712652, TOPMed rs562712652, gnomAD rs562712652, Uncertain significance
- D25N (p.Asp25Asn), rs562712652, ClinGen CA041649, ClinVar RCV001182968, ClinVar RCV002379705, CADD 9.18, PolyPhen-2 0.02, Conflicting interpretations, not specified; not provided; Cardiovascular phenotype
- D25D (p.Asp25Asp), gnomAD 19-11090678-C-T, CADD 9.55
- D25E (p.Asp25Glu), rs2077076517, gnomAD 19-11090678-C-A, CADD 8.96, SIFT 0.00
- D25Y (p.Asp25Tyr), gnomAD 19-11100228-G-T, MetaLR 0.67, MetaSVM -0.20
- R26* (p.Arg26Ter), rs879254398, ClinGen CA10584743, ClinVar RCV000238438, Ensembl rs879254398, Pathogenic
- R26K (p.Arg26Lys), rs1240034669, ClinGen CA404074593, ClinVar RCV004008182, gnomAD rs1240034669, CADD 0.82, PolyPhen-2 0.00, Uncertain significance, Hypercholesterolemia, familial, 1
- R26G (p.Arg26Gly), gnomAD 19-11090657-TC-T, CADD 3.04
- R26W (p.Arg26Trp), rs958077337, gnomAD 19-11090661-C-T, CADD 5.47, SIFT 0.00
- R26R (p.Arg26Arg), rs988636435, gnomAD 19-11090663-G-A, CADD 7.12
- R26C (p.Arg26Cys), gnomAD 19-11090667-C-T, CADD 6.71, SIFT 0.00
- R26H (p.Arg26His), rs576530433, gnomAD 19-11090668-G-A, CADD 0.74, SIFT 0.00
- C27* (p.Cys27Ter), rs2228671, ClinGen CA10584746, ClinVar RCV000237744, ClinVar RCV000775250, AlphaMissense 0.96, MetaLR 0.99, Pathogenic, in FHCL1
- C27R (p.Cys27Arg), rs1555802245, ClinGen CA404074603, ClinVar RCV000508969, ClinVar RCV001857282, CADD 27.10, PolyPhen-2 0.99, Likely pathogenic, Cardiovascular phenotype; Familial hypercholesterolemia; Hypercholesterolemia, f
- C27W (p.Cys27Trp), rs2228671, ClinGen CA041664, ClinVar RCV000211569, ClinVar RCV000588365, AlphaMissense 0.96, MetaLR 0.99, Pathogenic, Hypercholesterolemia, familial, 1
- C27Y (p.Cys27Tyr), rs1600700344, ClinGen CA404074606, ClinVar RCV002580826, Ensembl rs1600700344, AlphaMissense 0.96, MetaLR 0.99, Conflicting interpretations, Familial hypercholesterolemia; not provided
- C27C (p.Cys27Cys), rs2228671, gnomAD 19-11100236-C-T, AlphaMissense 0.96, MetaLR 0.99
- E28* (p.Glu28Ter), rs551747280, ClinGen CA10576267, ClinVar RCV000211620, 1000Genomes rs551747280, CADD 34.00, Pathogenic
- E28K (p.Glu28Lys), rs551747280, ClinGen CA041712, cosmic curated COSV10500, ClinVar RCV000495866, CADD 15.40, PolyPhen-2 0.24, Uncertain significance, Hypercholesterolemia, familial, 1
- E28G (p.Glu28Gly), gnomAD 19-11100238-A-G, MetaLR 0.50, MetaSVM -0.39
- R29* (p.Arg29Ter), rs879254401, ClinGen CA10584747, ClinVar RCV000238347, Ensembl rs879254401, Pathogenic
- R29T (p.Arg29Thr), TOPMed rs1193876749, CADD 16.90, PolyPhen-2 0.20, Uncertain significance, Familial hypercholesterolemia; not provided; Cardiovascular phenotype
- R29S (p.Arg29Ser), gnomAD 19-11090733-C-A, CADD 4.33, SIFT 0.00
- R29L (p.Arg29Leu), gnomAD 19-11090734-G-T, CADD 2.31, SIFT 0.00
- R29H (p.Arg29His), gnomAD 19-11090734-G-A, CADD 2.82, SIFT 0.00
- R29R (p.Arg29Arg), gnomAD 19-11090735-C-A, CADD 7.05
- R29Q (p.Arg29Gln), rs1273886653, gnomAD 19-11090749-G-A, CADD 2.85, SIFT 0.03
- R29I (p.Arg29Ile), gnomAD 19-11100241-G-T, MetaLR 0.83, MetaSVM 0.34
- N30K (p.Asn30Lys), rs72658855, ClinGen CA404074652, ClinVar RCV000521404, ClinVar RCV001273280, CADD 0.06, PolyPhen-2 0.17, Uncertain significance, not specified; Familial hypercholesterolemia; not provided
- N30N (p.Asn30Asn), rs72658855, gnomAD 19-11100245-C-T, CADD 1.02
- E31* (p.Glu31Ter), rs776421777, ClinGen CA10584748, ClinVar RCV000238408, ClinVar RCV001532988, AlphaMissense 0.31, MetaLR 0.89, Pathogenic
- E31G (p.Glu31Gly), cosmic curated COSV10457, 1000Genomes rs533807762, ExAC rs533807762, gnomAD rs533807762, CADD 27.60
- E31K (p.Glu31Lys), rs776421777, ClinGen CA041752, NCI-TCGA Cosmic COSV5294, cosmic curated COSV52941, AlphaMissense 0.31, MetaLR 0.89, Uncertain significance, Hypercholesterolemia, familial, 1
- E31V (p.Glu31Val), rs2077076613, gnomAD 19-11090686-A-T, CADD 11.70, SIFT 0.00
- E31D (p.Glu31Asp), rs535876665, gnomAD 19-11090687-G-T, CADD 8.08, SIFT 0.00
- F32C (p.Phe32Cys), rs879254403, ClinGen CA10584750, ClinVar RCV000238013, Ensembl rs879254403, AlphaMissense 1.00, MetaLR 0.98, Likely pathogenic, Hypercholesterolemia, familial, 1
- F32S (p.Phe32Ser), rs879254403, ClinGen CA305295205, ClinVar RCV001193786, ClinVar RCV002379750, AlphaMissense 1.00, MetaLR 0.98, Conflicting interpretations, Familial hypercholesterolemia; Hypercholesterolemia, familial, 1; Cardiovascular
- F32L (p.Phe32Leu), gnomAD 19-11090627-C-A, CADD 7.17, SIFT 0.00
- F32A (p.Phe32Ala), rs1305934975, gnomAD 19-11090729-TTTCC, CADD 7.90
- F32F (p.Phe32Phe), rs549017482, gnomAD 19-11100251-C-T, CADD 12.60
- Q33* (p.Gln33Ter), rs121908024, ClinGen CA023802, ClinVar RCV000003868, ClinVar RCV000786350, CADD 37.00, Pathogenic
- Q33R (p.Gln33Arg), rs759003630, gnomAD 19-11090635-A-G, CADD 10.30, SIFT 0.00
- Q33K (p.Gln33Lys), gnomAD 19-11090646-C-A, CADD 3.11, SIFT 0.00
- Q33Q (p.Gln33Gln), gnomAD 19-11100254-G-A, CADD 9.71
- C34* (p.Cys34Ter), rs879254407, ClinGen CA10584754, ClinVar RCV000237479, Ensembl rs879254407, AlphaMissense 0.99, MetaLR 1.00, Pathogenic
- C34G (p.Cys34Gly), rs879254405, ClinGen CA10584752, ClinVar RCV000237876, ClinVar RCV001230907, CADD 28.20, PolyPhen-2 1.00, Pathogenic/Likely pathogenic, Cardiovascular phenotype; Hypercholesterolemia, familial, 1; Familial hyperchole
- C34S (p.Cys34Ser), rs879254406, ClinGen CA10584753, ClinVar RCV000238421, Ensembl rs879254406, AlphaMissense 1.00, MetaLR 1.00, Likely pathogenic, Hypercholesterolemia, familial, 1
- C34W (p.Cys34Trp), rs879254407, ClinGen CA404074695, ClinVar RCV001450034, Ensembl rs879254407, AlphaMissense 0.99, MetaLR 1.00, Likely pathogenic, Hypercholesterolemia, familial, 1
- C34C (p.Cys34Cys), rs879254407, gnomAD 19-11100257-C-T, AlphaMissense 0.99, MetaLR 1.00
- Q35* (p.Gln35Ter), rs879254408, ClinGen CA10584755, ClinVar RCV000237937, ClinVar RCV001036722, Pathogenic
- Q35R (p.Gln35Arg), TOPMed rs2077193348, CADD 0.03, PolyPhen-2 0.00
- Q35P (p.Gln35Pro), gnomAD 19-11100259-A-C, MetaLR 0.54, MetaSVM -0.33
- Q35Q (p.Gln35Gln), gnomAD 19-11100260-A-G, CADD 4.86
- D36E (p.Asp36Glu), rs373144619, ClinGen CA10584756, ClinVar RCV000238476, ClinVar RCV001854882, CADD 4.53, PolyPhen-2 0.94, Conflicting interpretations, Cardiovascular phenotype; Familial hypercholesterolemia; Hypercholesterolemia, f
- D36Y (p.Asp36Tyr), rs2147210262, ClinGen CA404074706, ClinVar RCV002250090, NCI-TCGA TCGA novel, AlphaMissense 0.69, MetaLR 0.90, Pathogenic, Hypercholesterolemia, familial, 1
- D36V (p.Asp36Val), rs750945502, gnomAD 19-11100257-CCAAG, CADD 31.00
- D36H (p.Asp36His), gnomAD 19-11100261-G-C, MetaLR 0.90, MetaSVM 0.71
- D36D (p.Asp36Asp), rs373144619, gnomAD 19-11100263-C-T, CADD 0.52
- G37R (p.Gly37Arg), rs2077193497, ClinGen CA404074711, cosmic curated COSV52943, ClinVar RCV001187877, CADD 26.20, PolyPhen-2 0.78, Uncertain significance, Familial hypercholesterolemia; Hypercholesterolemia, familial, 1
- G37C (p.Gly37Cys), gnomAD 19-11090706-G-T, CADD 5.34, SIFT 0.00
- G37V (p.Gly37Val), rs2077077078, gnomAD 19-11090707-G-T, CADD 6.35, SIFT 0.00
- G37D (p.Gly37Asp), rs2077077078, gnomAD 19-11090707-G-A, CADD 6.86, SIFT 0.00
- G37G (p.Gly37Gly), gnomAD 19-11090708-C-T, CADD 6.49
- K38N (p.Lys38Asn), rs2147210320, ClinGen CA404074732, ClinVar RCV001923846, Ensembl rs2147210320, AlphaMissense 0.39, MetaLR 0.81, Uncertain significance, Familial hypercholesterolemia
- C39* (p.Cys39Ter), rs879254411, ClinGen CA10584759, ClinVar RCV000237239, Ensembl rs879254411, Pathogenic
- C39F (p.Cys39Phe), rs1131692189, ClinGen CA404074745, ClinVar RCV000495891, Ensembl rs1131692189, AlphaMissense 0.96, MetaLR 1.00, Pathogenic, Hypercholesterolemia, familial, 1
- C39R (p.Cys39Arg), rs1555802275, ClinGen CA404074738, ClinVar RCV000508808, ClinVar RCV001857283, CADD 28.60, PolyPhen-2 1.00, Conflicting interpretations, Cardiovascular phenotype; not provided; Hypercholesterolemia, familial, 1
- I40F (p.Ile40Phe), rs765969972, ClinGen CA404074754, ClinVar RCV003227425, AlphaMissense 0.20, MetaLR 0.91, Uncertain significance, not provided
- I40V (p.Ile40Val), rs765969972, ClinGen CA041837, ClinVar RCV000509299, ClinVar RCV001180282, AlphaMissense 0.20, MetaLR 0.91, Uncertain significance, Familial hypercholesterolemia; Hypercholesterolemia, familial, 1
- I40T (p.Ile40Thr), gnomAD 19-11090680-T-C, CADD 2.39, SIFT 0.00
- I40S (p.Ile40Ser), rs879254413, gnomAD 19-11100272-CA-C, CADD 27.90
- S41F (p.Ser41Phe), rs567126042, ClinGen CA305295229, cosmic curated COSV52943, ClinVar RCV001179044, CADD 25.10, PolyPhen-2 0.87, Uncertain significance, Familial hypercholesterolemia
- S41T (p.Ser41Thr), rs2077193859, ClinGen CA404074765, ClinVar RCV001122966, Ensembl rs2077193859, CADD 16.60, PolyPhen-2 0.04, Uncertain significance, Hypercholesterolemia, familial, 1
- S41P (p.Ser41Pro), rs1376762437, gnomAD 19-11090631-T-C, CADD 9.59, SIFT 0.00
- S41L (p.Ser41Leu), rs969190204, gnomAD 19-11090632-C-T, CADD 11.40, SIFT 0.00
- S41* (p.Ser41Ter), gnomAD 19-11090632-C-A, CADD 10.70
Public LDLR analysis runs
- LDLR analysis run — LDLR (2,294 variants) — completed 2026-08-10