LPA (Apolipoprotein(a)) variants and mutations
LPA (also known as Apolipoprotein(a)) is a human protein-coding gene encoding an apolipoprotein(a) protein. Its apolipoprotein(a) component covalently attaches to an LDL-like particle to form lipoprotein(a), whose circulating level is largely genetically determined. High Lp(a) is a causal risk factor for atherosclerotic cardiovascular disease and calcific aortic-valve disease. This analysis covers 2,741 LPA variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes cardiovascular disorder, coronary artery disorder, and myocardial infarction. Example LPA variants include M1?, H3L, and H3Y.
Variant analysis overview
- Gene: LPA
- Protein: Apolipoprotein(a)
- UniProt accession: P08519
- Organism: Homo sapiens
- Variants analyzed: 2741
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 2,518 unspecified-consequence records; 1 stop lost; 88 synonymous variants; 99 missense variants; 3 in-frame deletions; 7 stop-gained variants; 21 frameshift variants; 4 splice-region variants
- Prediction scores: 2,065 variants have prediction scores (75% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: cardiovascular disorder, coronary artery disorder, myocardial infarction, heart disorder, Hypercholesterolemia, atherosclerosis, hypertensive disorder, angina pectoris, myocardial ischemia, coronary atherosclerosis, peripheral vascular disease, metabolic disease.
Protein structure and variant hotspots
- Protein features: 17 domains; 17 post-translational modification sites.
- Structural context: 2,047 variants have structural context.
- PTM context: 16 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, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable LPA variants
Examples include M1?, H3L, H3Y, K4*, K4E, K4R, E5K, E5W. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; high impact.
- H3L (p.His3Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H3Y (p.His3Tyr), rs957300092, NCI-TCGA Cosmic COSV1003, TOPMed rs957300092, gnomAD rs957300092, REVEL 0.07, MetaLR 0.34, Variant assessed as somatic; moderate impact.
- K4* (p.Lys4Ter), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; high impact.
- K4E (p.Lys4Glu), gnomAD rs1282846608, REVEL 0.07, MetaLR 0.26
- K4R (p.Lys4Arg), TOPMed rs1031996107, gnomAD rs1031996107, REVEL 0.09, MetaLR 0.22
- E5K (p.Glu5Lys), NCI-TCGA TCGA novel, Ensembl rs1780271636, Variant assessed as somatic; moderate impact.
- E5W (p.Glu5Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V6A (p.Val6Ala), gnomAD rs1235491413, REVEL 0.16, MetaLR 0.41
- V7L (p.Val7Leu), gnomAD rs1353619698, REVEL 0.08, MetaLR 0.19
- L8F (p.Leu8Phe), TOPMed rs1482010159, gnomAD rs1482010159, REVEL 0.06, MetaLR 0.32
- L10P (p.Leu10Pro), TOPMed rs1252113389, gnomAD rs1252113389, REVEL 0.41, MetaLR 0.38
- L11F (p.Leu11Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L12S (p.Leu12Ser), Ensembl rs1780271325
- F13Y (p.Phe13Tyr), 1000Genomes rs559005335, ExAC rs559005335, gnomAD rs559005335, REVEL 0.12, MetaLR 0.23
- L14R (p.Leu14Arg), gnomAD rs1242379622, REVEL 0.45, MetaLR 0.37
- K15E (p.Lys15Glu), rs2484226403, ClinGen CA366351629, ClinVar RCV004410508, REVEL 0.13, MetaLR 0.15, Uncertain significance
- K15T (p.Lys15Thr), Ensembl rs1780270940
- A17G (p.Ala17Gly), TOPMed rs1403161561, gnomAD rs1403161561, REVEL 0.05, MetaLR 0.23
- A17T (p.Ala17Thr), TOPMed rs1780270850
- A17V (p.Ala17Val), TOPMed rs1403161561, gnomAD rs1403161561, REVEL 0.07, MetaLR 0.29
- A18T (p.Ala18Thr), NCI-TCGA Cosmic COSV6031, Ensembl rs1779985147, REVEL 0.21, MetaLR 0.37, Variant assessed as somatic; moderate impact.
- A18V (p.Ala18Val), ExAC rs748153271, gnomAD rs748153271, REVEL 0.18, MetaLR 0.29
- P19H (p.Pro19His), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- P19L (p.Pro19Leu), rs1188266967, NCI-TCGA Cosmic COSV1003, gnomAD rs1188266967, AlphaMissense 0.19, MetaLR 0.11, Variant assessed as somatic; moderate impact.
- P19R (p.Pro19Arg), gnomAD rs1188266967, REVEL 0.13, AlphaMissense 0.19
- P19S (p.Pro19Ser), gnomAD rs1779985045, REVEL 0.04, MetaLR 0.09
- Q21E (p.Gln21Glu), ExAC rs778710470, gnomAD rs778710470
- Q21K (p.Gln21Lys), NCI-TCGA Cosmic COSV6031, Variant assessed as somatic; moderate impact.
- S22C (p.Ser22Cys), TOPMed rs1779984814, REVEL 0.07, MetaLR 0.10
- S22N (p.Ser22Asn), ExAC rs754876758, gnomAD rs754876758, REVEL 0.03, MetaLR 0.06
- H23L (p.His23Leu), 1000Genomes rs570996250, ExAC rs570996250, TOPMed rs570996250, gnomAD rs570996250, REVEL 0.10, MetaLR 0.18, Uncertain significance
- H23Q (p.His23Gln), TOPMed rs1317484043, gnomAD rs1317484043, REVEL 0.08, MetaLR 0.09
- H23R (p.His23Arg), rs570996250, ClinGen CA4087208, ClinVar RCV004181039, 1000Genomes rs570996250, REVEL 0.07, MetaLR 0.14, Uncertain significance
- H23Y (p.His23Tyr), Ensembl rs1562352980, REVEL 0.15, MetaLR 0.19
- V24A (p.Val24Ala), 1000Genomes rs199786104, ExAC rs199786104, TOPMed rs199786104, REVEL 0.04, MetaLR 0.07
- V25I (p.Val25Ile), rs1779984391, ClinGen CA366349629, ClinVar RCV004361611, NCI-TCGA TCGA novel, REVEL 0.07, MetaLR 0.06, Uncertain significance
- Q26P (p.Gln26Pro), NCI-TCGA Cosmic COSV6031, Variant assessed as somatic; moderate impact.
- Q26R (p.Gln26Arg), gnomAD rs1265428461, REVEL 0.20, MetaLR 0.10
- D27E (p.Asp27Glu), TOPMed rs1337089315, gnomAD rs1337089315, REVEL 0.03, MetaLR 0.03
- D27N (p.Asp27Asn), NCI-TCGA Cosmic COSV6030, REVEL 0.08, MetaLR 0.09, Variant assessed as somatic; moderate impact.
- D27V (p.Asp27Val), TOPMed rs1219429589, gnomAD rs1219429589, REVEL 0.08, MetaLR 0.14
- D27Y (p.Asp27Tyr), TOPMed rs1473113079, gnomAD rs1473113079, REVEL 0.08, MetaLR 0.18
- C28Y (p.Cys28Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H30Q (p.His30Gln), NCI-TCGA Cosmic COSV6030, Variant assessed as somatic; moderate impact.
- H30R (p.His30Arg), rs1316313933, NCI-TCGA Cosmic COSV6030, gnomAD rs1316313933, REVEL 0.02, MetaLR 0.07, Variant assessed as somatic; moderate impact.
- H30Y (p.His30Tyr), ExAC rs751745914, gnomAD rs751745914, REVEL 0.07, MetaLR 0.07
- G31R (p.Gly31Arg), 1000Genomes rs183171143, ExAC rs183171143, TOPMed rs183171143, gnomAD rs183171143, REVEL 0.20, MetaLR 0.37, Uncertain significance
- G31S (p.Gly31Ser), rs183171143, ClinGen CA4087205, ClinVar RCV004321563, 1000Genomes rs183171143, REVEL 0.12, MetaLR 0.14, Uncertain significance
- D32N (p.Asp32Asn), ExAC rs763012249, gnomAD rs763012249, REVEL 0.04, MetaLR 0.02
- D32Y (p.Asp32Tyr), NCI-TCGA Cosmic COSV1003, NCI-TCGA Cosmic COSV6031, Variant assessed as somatic; moderate impact.
- Q34H (p.Gln34His), Ensembl rs1779983583
- Q34K (p.Gln34Lys), ESP rs370228332, ExAC rs370228332, TOPMed rs370228332, gnomAD rs370228332, REVEL 0.08, MetaLR 0.03
- S35N (p.Ser35Asn), TOPMed rs565044567, gnomAD rs565044567, REVEL 0.04, MetaLR 0.08
- S35R (p.Ser35Arg), 1000Genomes rs200491482, ExAC rs200491482, TOPMed rs200491482, gnomAD rs200491482, REVEL 0.13, MetaLR 0.25
- R37* (p.Arg37Ter), rs121912503, ClinGen CA123971, NCI-TCGA Cosmic COSV6029, ClinVar RCV000015535, CADD 35.00, Pathogenic
- R37G (p.Arg37Gly), rs121912503, NCI-TCGA Cosmic COSV6029, ExAC rs121912503, TOPMed rs121912503, REVEL 0.35, MetaLR 0.41, Pathogenic
- R37P (p.Arg37Pro), ExAC rs775410119, TOPMed rs775410119, gnomAD rs775410119
- R37Q (p.Arg37Gln), rs775410119, NCI-TCGA Cosmic COSV6029, ExAC rs775410119, TOPMed rs775410119, REVEL 0.16, MetaLR 0.14, Variant assessed as somatic; moderate impact.
- G38D (p.Gly38Asp), TOPMed rs1444990255, gnomAD rs1444990255, REVEL 0.57, MetaLR 0.91
- G38V (p.Gly38Val), TOPMed rs1444990255, gnomAD rs1444990255
- T39A (p.Thr39Ala), Ensembl rs1306126519
- T39M (p.Thr39Met), ESP rs376418933, ExAC rs376418933, TOPMed rs376418933, gnomAD rs376418933, REVEL 0.26, MetaLR 0.32
- T39R (p.Thr39Arg), ESP rs376418933, ExAC rs376418933, TOPMed rs376418933, gnomAD rs376418933, REVEL 0.33, MetaLR 0.24
- Y40* (p.Tyr40Ter), ExAC rs771773768, TOPMed rs771773768, gnomAD rs771773768, CADD 21.10
- Y40N (p.Tyr40Asn), Ensembl rs1562352927, REVEL 0.04, MetaLR 0.04
- T43A (p.Thr43Ala), Ensembl rs1779982688
- T43I (p.Thr43Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- T43S (p.Thr43Ser), ExAC rs747664654, gnomAD rs747664654, REVEL 0.33, MetaLR 0.38
- T45I (p.Thr45Ile), ExAC rs778426779, TOPMed rs778426779, gnomAD rs778426779, REVEL 0.25, MetaLR 0.20
- T45K (p.Thr45Lys), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- T45R (p.Thr45Arg), ExAC rs778426779, TOPMed rs778426779, gnomAD rs778426779
- G46R (p.Gly46Arg), ExAC rs768497880
- R47G (p.Arg47Gly), Ensembl rs1779982210
- C49W (p.Cys49Trp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C49Y (p.Cys49Tyr), 1000Genomes rs201060881, ExAC rs201060881, TOPMed rs201060881, gnomAD rs201060881, REVEL 0.52, MetaLR 0.91
- Q50* (p.Gln50Ter), TOPMed rs1779982038, gnomAD rs1779982038
- Q50E (p.Gln50Glu), TOPMed rs1779982038, gnomAD rs1779982038, REVEL 0.29, MetaLR 0.37
- A51T (p.Ala51Thr), rs779750198, NCI-TCGA Cosmic COSV6030, ExAC rs779750198, gnomAD rs779750198, REVEL 0.08, MetaLR 0.09, Variant assessed as somatic; moderate impact.
- A51V (p.Ala51Val), ExAC rs755876095, TOPMed rs755876095, gnomAD rs755876095, REVEL 0.20, MetaLR 0.13
- W52* (p.Trp52Ter), ExAC rs751841836, gnomAD rs751841836, CADD 35.00
- W52C (p.Trp52Cys), TOPMed rs1779981806, REVEL 0.51, MetaLR 0.92
- W52L (p.Trp52Leu), ExAC rs751841836, gnomAD rs751841836, REVEL 0.45, MetaLR 0.92
- W52S (p.Trp52Ser), ExAC rs751841836, gnomAD rs751841836
- S53L (p.Ser53Leu), rs777971266, NCI-TCGA Cosmic COSV6031, ExAC rs777971266, gnomAD rs777971266, REVEL 0.13, MetaLR 0.13, Variant assessed as somatic; moderate impact.
- S54P (p.Ser54Pro), ExAC rs765314362, TOPMed rs765314362, gnomAD rs765314362, REVEL 0.26, MetaLR 0.33
- M55L (p.Met55Leu), 1000Genomes rs375385826, ESP rs375385826, ExAC rs375385826, TOPMed rs375385826, REVEL 0.19, MetaLR 0.14
- M55V (p.Met55Val), 1000Genomes rs375385826, ESP rs375385826, ExAC rs375385826, TOPMed rs375385826, REVEL 0.19, MetaLR 0.15
- T56A (p.Thr56Ala), TOPMed rs1779981493
- T56I (p.Thr56Ile), TOPMed rs1299567827, gnomAD rs1299567827, REVEL 0.11, MetaLR 0.05
- P57Q (p.Pro57Gln), ExAC rs754339898, TOPMed rs754339898, gnomAD rs754339898, REVEL 0.32, MetaLR 0.42
- P57S (p.Pro57Ser), Ensembl rs1582899475
- H58N (p.His58Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H58P (p.His58Pro), TOPMed rs1377375128, gnomAD rs1377375128
- H58R (p.His58Arg), TOPMed rs1377375128, gnomAD rs1377375128, REVEL 0.26, MetaLR 0.33
- H58Y (p.His58Tyr), NCI-TCGA TCGA novel, REVEL 0.37, MetaLR 0.34, Variant assessed as somatic; moderate impact.
- Q59P (p.Gln59Pro), ExAC rs766900075, TOPMed rs766900075, gnomAD rs766900075
- Q59R (p.Gln59Arg), ExAC rs766900075, TOPMed rs766900075, gnomAD rs766900075, REVEL 0.05, MetaLR 0.03
- H60Y (p.His60Tyr), gnomAD rs1455915050
- N61D (p.Asn61Asp), TOPMed rs1396282902, gnomAD rs1396282902, REVEL 0.17, MetaLR 0.04
- N61S (p.Asn61Ser), rs191762721, ClinGen CA4087181, ClinVar RCV004229373, 1000Genomes rs191762721, REVEL 0.04, MetaLR 0.02, Uncertain significance
- R62G (p.Arg62Gly), ExAC rs771863444, TOPMed rs771863444, gnomAD rs771863444, REVEL 0.18, MetaLR 0.11
- R62S (p.Arg62Ser), TOPMed rs1779980745, REVEL 0.09, MetaLR 0.08
- R62T (p.Arg62Thr), ExAC rs761476925, gnomAD rs761476925
- R62W (p.Arg62Trp), ExAC rs771863444, TOPMed rs771863444, gnomAD rs771863444, REVEL 0.21, MetaLR 0.19
- T63I (p.Thr63Ile), Ensembl rs758644586
- T64I (p.Thr64Ile), TOPMed rs1779980645, gnomAD rs1779980645, REVEL 0.16, MetaLR 0.22
- E65K (p.Glu65Lys), NCI-TCGA Cosmic COSV6029, Variant assessed as somatic; moderate impact.
- E65V (p.Glu65Val), Ensembl rs1746618969
- Y67* (p.Tyr67Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P68L (p.Pro68Leu), NCI-TCGA Cosmic COSV1003, NCI-TCGA Cosmic COSV6030, Variant assessed as somatic; moderate impact.
- P68R (p.Pro68Arg), gnomAD rs1255140519, REVEL 0.33, MetaLR 0.28
- N69D (p.Asn69Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A70T (p.Ala70Thr), TOPMed rs967287601, gnomAD rs967287601, REVEL 0.30, MetaLR 0.28
- A70V (p.Ala70Val), rs544895795, NCI-TCGA Cosmic COSV6030, ExAC rs544895795, TOPMed rs544895795, REVEL 0.23, MetaLR 0.24, Variant assessed as somatic; moderate impact.
- D92Y (p.Asp92Tyr), gnomAD rs1339497082, REVEL 0.35, MetaLR 0.43
- V95I (p.Val95Ile), Ensembl rs112471977, REVEL 0.19, MetaLR 0.19
- E98G (p.Glu98Gly), gnomAD rs1291109525, REVEL 0.34, MetaLR 0.37
- T117I (p.Thr117Ile), Ensembl rs2115092697
- P120L (p.Pro120Leu), gnomAD rs200212358, REVEL 0.05, MetaLR 0.04
- S123N (p.Ser123Asn), gnomAD rs1399407878, REVEL 0.26, MetaLR 0.41
- L124V (p.Leu124Val), gnomAD rs1387786689
- E129F (p.Glu129Phe), gnomAD rs1457510235
- A131S (p.Ala131Ser), gnomAD rs1257893331, REVEL 0.18, MetaLR 0.06
- P132L (p.Pro132Leu), Ensembl rs146038804
- Q140R (p.Gln140Arg), Ensembl rs1554242304
- R151* (p.Arg151Ter), Ensembl rs1554242299
- Y154H (p.Tyr154His), Ensembl rs779534386
- V158L (p.Val158Leu), Ensembl rs1554242297
- A165V (p.Ala165Val), Ensembl rs201240804
- T177N (p.Thr177Asn), Ensembl rs1554242292
- G185D (p.Gly185Asp), Ensembl rs1779837591, REVEL 0.19, MetaLR 0.16
- I187L (p.Ile187Leu), Ensembl rs1779837482
- I187T (p.Ile187Thr), Ensembl rs1779837434
- N189K (p.Asn189Lys), Ensembl rs1779837330
- N189S (p.Asn189Ser), Ensembl rs1582894929
- N189T (p.Asn189Thr), Ensembl rs1582894929
- Y190* (p.Tyr190Ter), Ensembl rs1779837274
- C191R (p.Cys191Arg), Ensembl rs1779837224, REVEL 0.71, MetaLR 0.97
- N193D (p.Asn193Asp), Ensembl rs1779837084, REVEL 0.35, MetaLR 0.63
- N193I (p.Asn193Ile), 1000Genomes rs541612332, gnomAD rs541612332, REVEL 0.39, MetaLR 0.66
- N193S (p.Asn193Ser), 1000Genomes rs541612332, gnomAD rs541612332, REVEL 0.34, MetaLR 0.54
- P194L (p.Pro194Leu), ExAC rs762524065, gnomAD rs762524065, REVEL 0.39, MetaLR 0.69
- P194R (p.Pro194Arg), ExAC rs762524065, gnomAD rs762524065, REVEL 0.41, MetaLR 0.75
- D195G (p.Asp195Gly), Ensembl rs1779836829
- V197M (p.Val197Met), gnomAD rs1233089347, REVEL 0.14, MetaLR 0.13
- A198V (p.Ala198Val), gnomAD rs1369435281, REVEL 0.17, MetaLR 0.10
- A199D (p.Ala199Asp), Ensembl rs1779836580
- A199P (p.Ala199Pro), 1000Genomes rs1672519011, gnomAD rs1672519011, REVEL 0.24, MetaLR 0.22
- A199S (p.Ala199Ser), 1000Genomes rs1672519011, gnomAD rs1672519011, REVEL 0.19, MetaLR 0.08
- C202F (p.Cys202Phe), cosmic curated COSV60308, gnomAD rs1441807701, REVEL 0.47, MetaLR 0.81
- C202G (p.Cys202Gly), gnomAD rs1327998711, REVEL 0.48, MetaLR 0.81
- C202Y (p.Cys202Tyr), gnomAD rs1441807701, REVEL 0.43, MetaLR 0.81
- Y203* (p.Tyr203Ter), gnomAD rs771620931
- T204M (p.Thr204Met), gnomAD rs1327153515, REVEL 0.31, MetaLR 0.59
- T204R (p.Thr204Arg), gnomAD rs1327153515, REVEL 0.34, MetaLR 0.56
- R205S (p.Arg205Ser), Ensembl rs1779836179
- P207A (p.Pro207Ala), Ensembl rs1779836121, REVEL 0.24, MetaLR 0.32
- P207H (p.Pro207His), gnomAD rs1411897037, REVEL 0.25, MetaLR 0.39
- P207S (p.Pro207Ser), Ensembl rs1779836121, REVEL 0.23, MetaLR 0.21
- G208S (p.Gly208Ser), Ensembl rs1779835971, REVEL 0.11, MetaLR 0.02
- G208V (p.Gly208Val), Ensembl rs1779835901, REVEL 0.08, MetaLR 0.13
- V209A (p.Val209Ala), gnomAD rs1168299389, REVEL 0.30, MetaLR 0.27
- V209F (p.Val209Phe), Ensembl rs1779835855, REVEL 0.36, MetaLR 0.31
- R210G (p.Arg210Gly), gnomAD rs1453657874
- R210K (p.Arg210Lys), gnomAD rs1393269032
- R210S (p.Arg210Ser), Ensembl rs1779835609, REVEL 0.33, MetaLR 0.23
- R210T (p.Arg210Thr), gnomAD rs1393269032, REVEL 0.38, MetaLR 0.29
- W211C (p.Trp211Cys), Ensembl rs1779835564, REVEL 0.39, MetaLR 0.49
- E212D (p.Glu212Asp), gnomAD rs1194947191, REVEL 0.21, MetaLR 0.21
- Y213F (p.Tyr213Phe), Ensembl rs1779835465
- C214Y (p.Cys214Tyr), TOPMed rs1779835416
- L216R (p.Leu216Arg), Ensembl rs1562350210, REVEL 0.35, MetaLR 0.46
- T217K (p.Thr217Lys), TOPMed rs1779835311, REVEL 0.15, MetaLR 0.05
- T217M (p.Thr217Met), TOPMed rs1779835311, REVEL 0.13, MetaLR 0.16
- Q218E (p.Gln218Glu), gnomAD rs1454362755, REVEL 0.07, MetaLR 0.05
- D221G (p.Asp221Gly), gnomAD rs1231838924
- D221H (p.Asp221His), Ensembl rs1779835206, REVEL 0.12, MetaLR 0.20
- D221V (p.Asp221Val), gnomAD rs1231838924, REVEL 0.09, MetaLR 0.07
- A222P (p.Ala222Pro), Ensembl rs758985366, REVEL 0.10, MetaLR 0.09
Public LPA analysis runs
- LPA analysis run — LPA (2,741 variants) — completed 2026-08-18