ALPL (P05186) variants and mutations
ALPL (also known as P05186) is a human protein-coding gene encoding an alkaline phosphatase, tissue-nonspecific isozyme protein. It hydrolyzes extracellular pyrophosphate and other phosphate-containing substrates, enabling normal mineralization of bone and teeth. Loss-of-function variants cause hypophosphatasia, with severity ranging from lethal perinatal skeletal hypomineralization to adult fractures and dental disease. This analysis covers 1,006 ALPL variants and mutations. Of these, 73% have computational variant effect predictions. Disease context includes hypophosphatasia, infantile hypophosphatasia, and adult hypophosphatasia. Example ALPL variants include M1I, M1V, and I2N.
Variant analysis overview
- Gene: ALPL
- Protein: P05186
- UniProt accession: P05186
- Organism: Homo sapiens
- Variants analyzed: 1006
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 870 unspecified-consequence records; 67 synonymous variants; 45 missense variants; 4 in-frame deletions; 12 frameshift variants; 4 splice-region variants; 2 stop-gained variants; 2 substitution
- Prediction scores: 735 variants have prediction scores (73% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypophosphatasia, infantile hypophosphatasia, adult hypophosphatasia, odontohypophosphatasia, childhood hypophosphatasia, osteogenesis imperfecta, hereditary disease, ALPL-related autosomal recessive hypophosphatasia, perinatal lethal hypophosphatasia, nephrolithiasis, Decreased circulating alkaline phosphatase activity, ureterolithiasis.
Protein structure and variant hotspots
- Protein features: 14 binding sites; 6 post-translational modification sites.
- PTM context: 9 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 ALPL variants
Examples include M1I, M1V, I2N, I2T, I2V, S3S, S3N, S3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1362833043, ClinGen CA338876288, ClinVar RCV003547080, MetaLR 0.71, MetaSVM 0.23, Pathogenic, Hypophosphatasia
- M1V (p.Met1Val), rs2148135255, ClinGen CA338876282, ClinVar RCV001897390, ClinVar RCV005016734, MetaLR 0.72, MetaSVM 0.31, Uncertain significance, Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia
- I2N (p.Ile2Asn), TOPMed rs1644366657, REVEL 0.42, CADD 23.70
- I2T (p.Ile2Thr), TOPMed rs1644366657, REVEL 0.39, CADD 22.30, Uncertain significance, Inborn genetic diseases
- I2V (p.Ile2Val), Ensembl rs776442538, REVEL 0.17, CADD 18.80
- S3S (p.Ser3Ser), rs749406361, gnomAD 1-21554090-A-T, CADD 8.82
- S3N (p.Ser3Asn), gnomAD 1-21560690-G-A, CADD 2.10
- S3L (p.Ser3Leu), gnomAD 1-21560702-C-T, CADD 9.60
- S3* (p.Ser3Ter), rs1644471877, gnomAD 1-21560702-C-G, CADD 8.40
- P4L (p.Pro4Leu), gnomAD 1-21554092-C-T, REVEL 0.24, CADD 13.80
- P4P (p.Pro4Pro), rs771198723, gnomAD 1-21554093-A-G, CADD 6.62
- F5S (p.Phe5Ser), gnomAD 1-21554095-T-C, REVEL 0.60, CADD 23.10
- F5F (p.Phe5Phe), gnomAD 1-21554096-C-T, CADD 12.40
- F5L (p.Phe5Leu), gnomAD 1-21554096-C-A, REVEL 0.23, CADD 18.10
- V7L (p.Val7Leu), TOPMed rs1034151595, gnomAD rs1034151595, REVEL 0.28, CADD 13.60, Uncertain significance, not provided
- V7I (p.Val7Ile), gnomAD 1-21554100-G-A, REVEL 0.21, CADD 15.00
- V7V (p.Val7Val), rs2148135312, gnomAD 1-21554102-A-G, CADD 8.18
- L8V (p.Leu8Val), rs774559268, ClinGen CA19083720, ClinVar RCV002633015, ExAC rs774559268, REVEL 0.51, CADD 19.20, Uncertain significance, not provided
- L8del (p.Leu8del), gnomAD 1-21554100-GTAC-G, CADD 17.20
- L8L (p.Leu8Leu), rs774559268, gnomAD 1-21554103-C-T, CADD 8.97
- A9S (p.Ala9Ser), rs759760207, ClinGen CA666359, ClinVar RCV003349847, ExAC rs759760207, REVEL 0.28, CADD 19.50, Uncertain significance, Inborn genetic diseases
- A9V (p.Ala9Val), rs772679576, ClinGen CA666360, ClinVar RCV001101710, ClinVar RCV002480471, REVEL 0.25, CADD 17.50, Uncertain significance, Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia
- A9W (p.Ala9Trp), gnomAD 1-21554105-GGCCAT, CADD 26.20
- I10F (p.Ile10Phe), TOPMed rs987088751, gnomAD rs987088751, REVEL 0.43, CADD 13.80
- I10T (p.Ile10Thr), rs1408044973, ClinGen CA338876368, cosmic curated COSV66380, ClinVar RCV003317753, REVEL 0.31, CADD 21.10, Likely pathogenic, Hypophosphatasia
- I10V (p.Ile10Val), TOPMed rs987088751, gnomAD rs987088751, REVEL 0.32, CADD 8.01
- G11D (p.Gly11Asp), rs1287863636, ClinGen CA338876382, ClinVar RCV003834392, gnomAD rs1287863636, REVEL 0.61, CADD 19.30, Uncertain significance, Inborn genetic diseases; not provided
- G11V (p.Gly11Val), gnomAD 1-21554113-G-T, REVEL 0.60, CADD 20.70
- G11G (p.Gly11Gly), rs1558543098, gnomAD 1-21554114-C-T, CADD 4.18
- T12I (p.Thr12Ile), rs1570252164, ClinGen CA338876398, ClinVar RCV001348759, Ensembl rs1570252164, REVEL 0.25, CADD 15.20, Uncertain significance, not provided
- T12P (p.Thr12Pro), TOPMed rs1432384649
- T12M (p.Thr12Met), rs539884496, gnomAD 1-21560711-C-T, CADD 0.59
- C13* (p.Cys13Ter), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10087, Variant assessed as somatic; high impact.
- p.Cys13 Ser17del, gnomAD 1-21554115-ACCTGC, CADD 17.20
- L14F (p.Leu14Phe), rs139214514, ClinGen CA666361, ClinVar RCV000442772, ClinVar RCV001277094, REVEL 0.26, CADD 15.90, Uncertain significance, not specified; not provided
- L14P (p.Leu14Pro), rs2148135377, ClinGen CA338876432, ClinVar RCV001815056, Ensembl rs2148135377, AlphaMissense 0.16, MetaLR 0.84, Conflicting interpretations, Hypophosphatasia
- T15P (p.Thr15Pro), gnomAD rs1241484434, REVEL 0.52, CADD 15.40
- T15S (p.Thr15Ser), rs150849772, ClinGen CA666362, ClinVar RCV000916215, ClinVar RCV001832071, REVEL 0.34, CADD 7.22, Likely benign, Hypophosphatasia; not provided
- N16N (p.Asn16Asn), rs1039403484, gnomAD 1-21554129-C-T, CADD 7.62
- S17F (p.Ser17Phe), cosmic curated COSV10654, UniProt VAR 025903, Pathogenic/Likely pathogenic, Hypophosphatasia
- S17S (p.Ser17Ser), gnomAD 1-21554132-C-G, CADD 5.56
- L18I (p.Leu18Ile), gnomAD rs1221539606, REVEL 0.20, CADD 13.50
- P20P (p.Pro20Pro), rs925035427, gnomAD 1-21554141-A-C, CADD 22.20
- E21K (p.Glu21Lys), rs1553410728, ClinGen CA338876534, ClinVar RCV000672433, ClinVar RCV005645148, AlphaMissense 0.12, MetaLR 0.82, Conflicting interpretations, not provided; Hypophosphatasia
- E21R (p.Glu21Arg), gnomAD 1-21554140-C-CA, CADD 25.30
- E21* (p.Glu21Ter), gnomAD 1-21554142-G-T, CADD 45.00
- E23E (p.Glu23Glu), rs912257857, gnomAD 1-21560633-G-A, CADD 8.59
- K24E (p.Lys24Glu), gnomAD 1-21560634-A-G, REVEL 0.52, CADD 20.20
- D25N (p.Asp25Asn), rs766948855, NCI-TCGA Cosmic COSV1008, cosmic curated COSV10087, NCI-TCGA Cosmic COSV6637, REVEL 0.32, CADD 18.10, Variant assessed as somatic; moderate impact.
- D25Y (p.Asp25Tyr), NCI-TCGA Cosmic COSV1008, NCI-TCGA Cosmic COSV6637, cosmic curated COSV66379, Variant assessed as somatic; moderate impact.
- D25D (p.Asp25Asp), rs1428307986, gnomAD 1-21560639-C-T, CADD 8.07
- D25E (p.Asp25Glu), gnomAD 1-21560639-C-A, REVEL 0.29, CADD 15.80
- P26H (p.Pro26His), cosmic curated COSV66379, gnomAD rs1170372723, REVEL 0.81, CADD 25.10
- P26L (p.Pro26Leu), NCI-TCGA Cosmic COSV6637, NCI-TCGA Cosmic COSV6638, cosmic curated COSV66380, Uncertain significance, Hypophosphatasia
- P26S (p.Pro26Ser), gnomAD 1-21560640-C-T, REVEL 0.72, CADD 23.70
- P26P (p.Pro26Pro), rs375342528, gnomAD 1-21560642-C-T, CADD 8.05
- K27E (p.Lys27Glu), NCI-TCGA Cosmic COSV6637, cosmic curated COSV66379, Ensembl rs1644469548, Uncertain significance, Childhood hypophosphatasia; Adult hypophosphatasia; Infantile hypophosphatasia
- K27N (p.Lys27Asn), TOPMed rs1644469640, gnomAD rs1644469640, REVEL 0.17, CADD 10.10, Uncertain significance, not provided
- K27R (p.Lys27Arg), ESP rs146412299, ExAC rs146412299, TOPMed rs146412299, gnomAD rs146412299, REVEL 0.25, CADD 15.40
- Y28C (p.Tyr28Cys), UniProt VAR 013972, REVEL 0.91, CADD 24.90, Pathogenic, Hypophosphatasia
- W29* (p.Trp29Ter), rs1553411779, ClinGen CA338877483, ClinVar RCV000666764, ClinVar RCV005091931, Pathogenic
- R30* (p.Arg30Ter), rs1057516334, ClinGen CA16040712, NCI-TCGA Cosmic COSV6638, cosmic curated COSV66380, AlphaMissense 0.34, MetaLR 0.80, Pathogenic
- R30G (p.Arg30Gly), rs1057516334, ClinGen CA338877486, ClinVar RCV001772511, ClinVar RCV005645294, AlphaMissense 0.34, MetaLR 0.80, Uncertain significance, not provided; Hypophosphatasia
- R30Q (p.Arg30Gln), rs753550135, NCI-TCGA Cosmic COSV6637, cosmic curated COSV66379, ExAC rs753550135, REVEL 0.43, CADD 22.90, Uncertain significance, Adult hypophosphatasia
- D31G (p.Asp31Gly), Ensembl rs1644469923
- D31H (p.Asp31His), cosmic curated COSV10469
- D31N (p.Asp31Asn), rs757127456, ClinGen CA666393, ClinVar RCV001979535, ExAC rs757127456, REVEL 0.14, CADD 1.29, Uncertain significance, not provided
- Q32* (p.Gln32Ter), rs1209147330, ClinGen CA338877498, ClinVar RCV001251316, ClinVar RCV002568714, CADD 34.00, Pathogenic
- Q32R (p.Gln32Arg), Ensembl rs2148150929
- A33G (p.Ala33Gly), rs121918005, ClinGen CA666394, ClinVar RCV003665437, ExAC rs121918005, REVEL 0.73, CADD 22.70, Likely pathogenic, not provided
- A33P (p.Ala33Pro), rs1315428192, ClinVar RCV004586137, AlphaMissense 0.86, MetaLR 0.92, Uncertain significance, not specified
- A33T (p.Ala33Thr), gnomAD rs1315428192
- A33V (p.Ala33Val), rs121918005, ClinGen CA256924, ClinVar RCV000014655, ClinVar RCV001042961, REVEL 0.87, CADD 23.70, Pathogenic/Likely pathogenic, Childhood hypophosphatasia; Infantile hypophosphatasia; Adult hypophosphatasia
- A33A (p.Ala33Ala), rs772424729, gnomAD 1-21560663-G-A, CADD 2.63
- Q34R (p.Gln34Arg), ExAC rs780221572
- E35D (p.Glu35Asp), gnomAD 1-21560669-G-C, REVEL 0.29, CADD 16.60
- E35E (p.Glu35Glu), gnomAD 1-21560669-G-A, CADD 6.19
- T36A (p.Thr36Ala), ExAC rs747167000, gnomAD rs747167000, Uncertain significance, Inborn genetic diseases
- T36I (p.Thr36Ile), rs199952414, ClinGen CA10609815, ClinVar RCV000309784, ClinVar RCV005090425, REVEL 0.62, CADD 23.50, Conflicting interpretations, Hypophosphatasia; not provided
- T36P (p.Thr36Pro), rs747167000, ClinGen CA338877523, ClinVar RCV001813915, ClinVar RCV003728016, REVEL 0.80, CADD 24.00, Conflicting interpretations, not provided; Hypophosphatasia; Hypophosphataemia or rickets
- T36T (p.Thr36Thr), rs1308077007, gnomAD 1-21560672-A-C, CADD 3.56
- L37P (p.Leu37Pro), rs143358506, ClinGen CA19088076, ClinVar RCV002630052, ClinVar RCV003475519, REVEL 0.94, CADD 25.20, Pathogenic/Likely pathogenic, Hypophosphatasia; Adult hypophosphatasia; not provided
- L37L (p.Leu37Leu), rs1205971311, gnomAD 1-21560673-C-T, CADD 6.38
- Y39C (p.Tyr39Cys), rs777235122, ClinGen CA666399, ClinVar RCV003141340, ExAC rs777235122, MetaLR 0.78, MetaSVM 0.62, Uncertain significance, not specified; not provided
- A40G (p.Ala40Gly), ExAC rs770093969, TOPMed rs770093969, gnomAD rs770093969, Pathogenic, in HOPS
- A40S (p.Ala40Ser), gnomAD rs1455153945, Likely pathogenic, in HOPS
- A40T (p.Ala40Thr), rs1455153945, ClinGen CA338877546, NCI-TCGA Cosmic COSV6638, cosmic curated COSV66380, AlphaMissense 0.28, MetaLR 0.78, Likely pathogenic, not provided
- A40V (p.Ala40Val), rs770093969, ClinGen CA666401, ClinVar RCV001253054, ClinVar RCV001264416, REVEL 0.79, CADD 22.70, Pathogenic/Likely pathogenic, not provided; Hypophosphatasia; Adult hypophosphatasia
- A40D (p.Ala40Asp), gnomAD 1-21560683-C-A, REVEL 0.84, CADD 23.80
- E42K (p.Glu42Lys), cosmic curated COSV10654, Ensembl rs1558547291, Uncertain significance, not provided
- L43F (p.Leu43Phe), ESP rs148357203, TOPMed rs148357203, gnomAD rs148357203, REVEL 0.51, CADD 24.50, Conflicting interpretations, not provided; Adult hypophosphatasia
- Q44* (p.Gln44Ter), Ensembl rs1057516293, CADD 36.00, Pathogenic
- Q44E (p.Gln44Glu), NCI-TCGA Cosmic COSV6638, cosmic curated COSV66380, Variant assessed as somatic; moderate impact.
- Q44R (p.Gln44Arg), rs763244290, gnomAD 1-21560691-CT-C, CADD 25.90
- K45R (p.Lys45Arg), Ensembl rs1644471781, REVEL 0.14, CADD 13.80
- L46F (p.Leu46Phe), gnomAD 1-21560700-C-T, REVEL 0.45, CADD 20.20
- L46P (p.Leu46Pro), gnomAD 1-21560701-T-C, REVEL 0.70, CADD 24.10
- N47I (p.Asn47Ile), rs2148151094, ClinGen CA338877610, ClinVar RCV001815059, ClinVar RCV005409022, AlphaMissense 0.62, MetaLR 0.79, Likely pathogenic, not provided
- N47S (p.Asn47Ser), cosmic curated COSV66380, REVEL 0.37, CADD 19.90, Uncertain significance, Infantile hypophosphatasia
- N47D (p.Asn47Asp), gnomAD 1-21560703-A-G, REVEL 0.59, CADD 22.60
- T48I (p.Thr48Ile), rs1430855435, ClinGen CA338877617, ClinVar RCV002653183, TOPMed rs1430855435, AlphaMissense 0.08, MetaLR 0.77, Uncertain significance, not provided
- T48S (p.Thr48Ser), TOPMed rs1430855435, gnomAD rs1430855435, REVEL 0.31, AlphaMissense 0.08, Uncertain significance, not provided
- N49D (p.Asn49Asp), Ensembl rs1644471991, Conflicting interpretations, Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia
- N49I (p.Asn49Ile), rs868522953, ClinGen CA338877627, ClinVar RCV001818095, TOPMed rs868522953, AlphaMissense 0.64, MetaLR 0.67, Conflicting interpretations, Hypophosphatasia
- N49K (p.Asn49Lys), 1000Genomes rs539884496, ExAC rs539884496, TOPMed rs539884496, gnomAD rs539884496, REVEL 0.24, CADD 0.26, Likely benign
- N49S (p.Asn49Ser), rs868522953, ClinGen CA19088109, ClinVar RCV003870471, ClinVar RCV004701857, REVEL 0.36, AlphaMissense 0.64, Conflicting interpretations, Hypophosphatasia; not specified
- V50M (p.Val50Met), ExAC rs767216554, TOPMed rs767216554, gnomAD rs767216554, REVEL 0.35, CADD 23.80, Uncertain significance, not specified; not provided
- V50G (p.Val50Gly), gnomAD 1-21560713-T-G, REVEL 0.50, CADD 22.80
- A51S (p.Ala51Ser), UniProt VAR 025904, Conflicting interpretations, Hypophosphatasia; not specified
- A51V (p.Ala51Val), rs1470389268, UniProt VAR 013973, gnomAD rs1470389268, REVEL 0.86, CADD 24.00, Pathogenic/Likely pathogenic, Hypophosphatasia; not provided; Adult hypophosphatasia
- K52R (p.Lys52Arg), gnomAD 1-21560719-A-G, REVEL 0.57, CADD 22.50
- N53K (p.Asn53Lys), ExAC rs774859071, gnomAD rs774859071, REVEL 0.73, CADD 14.70
- V54F (p.Val54Phe), Ensembl rs2148151181
- I55V (p.Ile55Val), TOPMed rs963835902, gnomAD rs963835902, REVEL 0.47, CADD 22.20, Uncertain significance, not provided
- I55del (p.Ile55del), rs766831104, gnomAD 1-21560724-GTCA-G, CADD 21.60
- I55L (p.Ile55Leu), gnomAD 1-21560727-A-C, REVEL 0.79, CADD 24.60
- M56L (p.Met56Leu), ExAC rs760272172, TOPMed rs760272172, gnomAD rs760272172, Uncertain significance, Childhood hypophosphatasia; Adult hypophosphatasia; Infantile hypophosphatasia
- M56T (p.Met56Thr), rs1288112235, ClinGen CA338877703, ClinVar RCV003659443, ClinVar RCV004985459, AlphaMissense 0.21, MetaLR 0.85, Uncertain significance, Inborn genetic diseases; not provided
- M56V (p.Met56Val), ExAC rs760272172, TOPMed rs760272172, gnomAD rs760272172, Uncertain significance, not specified; not provided
- F57Y (p.Phe57Tyr), ExAC rs763919659, gnomAD rs763919659
- L58M (p.Leu58Met), TOPMed rs867333918, gnomAD rs867333918, Likely benign
- L58P (p.Leu58Pro), rs2545290283, ClinGen CA338877730, ClinVar RCV003991958, Likely pathogenic, Adult hypophosphatasia
- L58L (p.Leu58Leu), rs867333918, gnomAD 1-21560736-C-T, CADD 11.00
- G59E (p.Gly59Glu), rs925157796, ClinGen CA19088185, ClinVar RCV003448555, ClinVar RCV003708802, REVEL 0.99, CADD 29.00, Conflicting interpretations, not provided; Hypophosphatasia
- D60H (p.Asp60His), rs1644472852, ClinGen CA338877755, ClinVar RCV001351723, ClinVar RCV001822864, AlphaMissense 0.99, MetaLR 0.81, Conflicting interpretations, not provided; Adult hypophosphatasia; Hypophosphatasia
- G61E (p.Gly61Glu), rs2545291966, ClinGen CA338877824, ClinVar RCV002843244, ClinVar RCV005645411, Likely pathogenic, not provided; Hypophosphatasia
- G61R (p.Gly61Arg), rs2148151280, ClinGen CA338877769, ClinVar RCV001995386, Ensembl rs2148151280, AlphaMissense 0.99, MetaLR 0.85, Uncertain significance, not provided
- G61W (p.Gly61Trp), cosmic curated COSV66380
- M62I (p.Met62Ile), Ensembl rs2148152244, REVEL 0.96, CADD 26.00, Likely pathogenic, Hypophosphatasia
- M62L (p.Met62Leu), rs1644478213, ClinGen CA338877833, ClinVar RCV003412871, ClinVar RCV005645478, AlphaMissense 0.76, MetaLR 0.98, Conflicting interpretations, not provided; Hypophosphatasia
- M62V (p.Met62Val), Ensembl rs1644478213, UniProt VAR 025905, REVEL 0.97, AlphaMissense 0.76, Likely pathogenic, Hypophosphatasia
- G63C (p.Gly63Cys), rs2545291979, ClinGen CA338877845, ClinVar RCV003690247, REVEL 0.98, CADD 32.00, Likely pathogenic, not provided
- G63D (p.Gly63Asp), gnomAD rs1490668038, REVEL 0.97, CADD 26.80, Likely pathogenic, in HOPS
- G63R (p.Gly63Arg), UniProt VAR 025906, Likely pathogenic, Hypophosphatasia
- G63V (p.Gly63Val), rs1490668038, ClinGen CA338877852, ClinVar RCV000595916, ClinVar RCV005010577, REVEL 0.99, CADD 28.10, Pathogenic/Likely pathogenic, Hypophosphatasia; not provided; Childhood hypophosphatasia
- G63G (p.Gly63Gly), rs1570269466, gnomAD 1-21561104-T-G, CADD 5.04
- V64L (p.Val64Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V64I (p.Val64Ile), gnomAD 1-21561105-G-A, REVEL 0.44, CADD 20.20
- S65F (p.Ser65Phe), TOPMed rs1644478359, Likely pathogenic
- S65Y (p.Ser65Tyr), rs1644478359, ClinGen CA338877872, ClinVar RCV001815061, TOPMed rs1644478359, AlphaMissense 0.95, MetaLR 0.96, Conflicting interpretations, Hypophosphatasia
- S65C (p.Ser65Cys), gnomAD 1-21561109-C-G, REVEL 0.90, CADD 26.60
- T66I (p.Thr66Ile), gnomAD rs1249754841, REVEL 0.94, CADD 26.60, Uncertain significance, not provided
- T66K (p.Thr66Lys), gnomAD 1-21561112-C-A, REVEL 0.94, CADD 26.00
- T68M (p.Thr68Met), rs1644478533, ClinGen CA338877904, cosmic curated COSV10087, ClinVar RCV001389815, REVEL 0.97, CADD 25.30, Pathogenic/Likely pathogenic, not provided; Hypophosphatasia; Adult hypophosphatasia
- T68T (p.Thr68Thr), rs537814225, gnomAD 1-21561119-G-A, CADD 0.47
- A69T (p.Ala69Thr), gnomAD rs1178008018, Likely pathogenic, Hypophosphatasia
- A69V (p.Ala69Val), rs2545292067, ClinVar RCV004586512, Uncertain significance, Hypophosphatasia
- A70T (p.Ala70Thr), rs147116628, ClinGen CA666433, ClinVar RCV001768828, ESP rs147116628, REVEL 0.47, CADD 16.90, Uncertain significance, not provided
- A70A (p.Ala70Ala), gnomAD 1-21561125-C-G, CADD 7.99
- R71C (p.Arg71Cys), rs121918001, ClinGen CA256920, ClinVar RCV000014649, ClinVar RCV001851857, REVEL 0.99, CADD 27.40, Pathogenic, not provided; Hypophosphatasia; Adult hypophosphatasia
- R71G (p.Arg71Gly), rs121918001, ClinGen CA338877926, ClinVar RCV003562213, ClinVar RCV005645502, REVEL 0.99, CADD 25.60, Pathogenic/Likely pathogenic, Hypophosphatasia; not provided
- R71H (p.Arg71His), rs121918003, ClinGen CA19088467, cosmic curated COSV66379, ClinVar RCV001382221, REVEL 0.97, CADD 29.10, Pathogenic, Hypophosphatasia; Adult hypophosphatasia; Childhood hypophosphatasia
- R71L (p.Arg71Leu), cosmic curated COSV66380
- R71P (p.Arg71Pro), rs121918003, ClinGen CA256922, ClinVar RCV000014653, ClinVar RCV001362179, REVEL 0.99, CADD 31.00, Pathogenic/Likely pathogenic, not provided; Hypophosphatasia; Adult hypophosphatasia
- R71S (p.Arg71Ser), rs121918001, ClinGen CA666434, ClinVar RCV003476483, ClinVar RCV003553956, REVEL 0.96, CADD 25.30, Pathogenic/Likely pathogenic, not provided; Hypophosphatasia; Adult hypophosphatasia
- R71A (p.Arg71Ala), gnomAD 1-21561123-GC-G, CADD 26.90
- R71R (p.Arg71Arg), gnomAD 1-21561128-C-T, CADD 7.15
- I72T (p.Ile72Thr), rs781264043, ClinGen CA274142, ClinVar RCV000169295, ClinVar RCV001204937, REVEL 0.94, CADD 27.30, Pathogenic/Likely pathogenic, Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia
- I72V (p.Ile72Val), rs2148152364, ClinGen CA338877933, ClinVar RCV001815064, ClinVar RCV004762189, AlphaMissense 0.34, MetaLR 0.90, Pathogenic/Likely pathogenic, not provided; Hypophosphatasia; Adult hypophosphatasia
- I72I (p.Ile72Ile), rs1644478962, gnomAD 1-21561131-C-A, CADD 11.40
- L73del (p.Leu73del), rs2148152384, gnomAD 1-21561129-ATCC-A, CADD 20.50
- L73L (p.Leu73Leu), rs1364859151, gnomAD 1-21561134-C-T, CADD 12.50
- K74N (p.Lys74Asn), cosmic curated COSV10087
- K74R (p.Lys74Arg), ESP rs143885304, ExAC rs143885304, TOPMed rs143885304, gnomAD rs143885304, REVEL 0.72, CADD 26.30
- G75S (p.Gly75Ser), rs1304394441, ClinGen CA338877969, ClinVar RCV001382222, ClinVar RCV003469672, REVEL 0.98, CADD 29.50, Pathogenic/Likely pathogenic, not provided; Hypophosphatasia; Adult hypophosphatasia
- G75G (p.Gly75Gly), gnomAD 1-21561140-T-C, CADD 7.84
- Q76* (p.Gln76Ter), rs1333485956, ClinGen CA338877981, ClinVar RCV003461858, ClinVar RCV005021973, Pathogenic, in HOPS
- Q76R (p.Gln76Arg), rs1057521085, ClinGen CA16603529, ClinVar RCV000418683, ClinVar RCV002278676, REVEL 0.96, CADD 27.60, Pathogenic/Likely pathogenic, not provided; Adult hypophosphatasia; Hypophosphatasia
- H78Q (p.His78Gln), TOPMed rs1375160574, gnomAD rs1375160574, REVEL 0.32, CADD 15.40
- H78Y (p.His78Tyr), rs1279759337, ClinGen CA338878005, ClinVar RCV002996682, gnomAD rs1279759337, REVEL 0.38, CADD 23.30, Uncertain significance, not provided
- H78H (p.His78His), rs1375160574, gnomAD 1-21561149-C-T, CADD 10.60
- H79R (p.His79Arg), gnomAD 1-21561151-A-G, REVEL 0.36, CADD 23.40
- H79H (p.His79His), rs1644479451, gnomAD 1-21561152-C-T, CADD 10.70
- N80K (p.Asn80Lys), ExAC rs756611513, gnomAD rs756611513, REVEL 0.26, CADD 7.90
- N80S (p.Asn80Ser), TOPMed rs991273242, gnomAD rs991273242, REVEL 0.19, CADD 9.40
- P81S (p.Pro81Ser), rs915866721, ClinGen CA19088495, cosmic curated COSV66379, ClinVar RCV001996353, REVEL 0.28, CADD 7.32, Uncertain significance, Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia
- P81P (p.Pro81Pro), gnomAD 1-21561158-T-C, CADD 3.61
- G82E (p.Gly82Glu), rs2148152529, ClinGen CA338878061, ClinVar RCV001760487, Ensembl rs2148152529, AlphaMissense 0.96, MetaLR 0.95, Uncertain significance, not provided
- G82R (p.Gly82Arg), rs2545292224, ClinGen CA338878055, ClinVar RCV003447660, ClinGen CA338878058, Pathogenic/Likely pathogenic, Hypophosphatasia
- G82G (p.Gly82Gly), rs1644479721, gnomAD 1-21561161-G-A, CADD 8.89
Public ALPL analysis runs
- ALPL analysis run — ALPL (1,006 variants) — completed 2026-08-19