PCSK1 (Neuroendocrine convertase 1) variants and mutations
PCSK1 (also known as Neuroendocrine convertase 1) is a human protein-coding gene encoding a neuroendocrine convertase 1 protein. It activates numerous peptide hormones and neuropeptides by cleaving their precursor proteins in endocrine and neuroendocrine secretory granules. Biallelic loss-of-function variants can cause severe early-onset obesity, endocrine abnormalities, and malabsorptive diarrhea. This analysis covers 1,097 PCSK1 variants and mutations. Of these, 95% have computational variant effect predictions. Disease context includes obesity due to prohormone convertase I deficiency, Abnormality of the skeletal system, and obesity disorder. Example PCSK1 variants include M1?, E2D, and E2K.
Variant analysis overview
- Gene: PCSK1
- Protein: Neuroendocrine convertase 1
- UniProt accession: P29120
- Organism: Homo sapiens
- Variants analyzed: 1097
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 816 unspecified-consequence records; 119 synonymous variants; 134 missense variants; 9 frameshift variants; 8 in-frame deletions; 6 stop-gained variants; 2 in-frame insertions; 1 splice-region variants; 2 substitution
- Prediction scores: 1,039 variants have prediction scores (95% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: obesity due to prohormone convertase I deficiency, Abnormality of the skeletal system, obesity disorder, gestational diabetes, osteoarthritis, knee, aneurysm, aortic aneurysm, smoking initiation, obesity due to melanocortin 4 receptor deficiency, osteoarthritis, hip, type 2 diabetes mellitus, frozen shoulder.
Protein structure and variant hotspots
- Protein features: 2 domains; 3 post-translational modification sites.
- Structural context: 599 variants have structural context.
- PTM context: 3 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, MaveDB, LitVar.
Notable PCSK1 variants
Examples include M1?, E2D, E2K, R3L, R3Q, W6R, S7G, Q9H. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E2D (p.Glu2Asp), NCI-TCGA TCGA novel, MetaLR 0.19, MetaSVM -0.90, Variant assessed as somatic; moderate impact.
- E2K (p.Glu2Lys), ExAC rs773338510, gnomAD rs773338510, REVEL 0.12, MetaLR 0.18
- R3L (p.Arg3Leu), ExAC rs767413349, gnomAD rs767413349, REVEL 0.07, MetaLR 0.08
- R3Q (p.Arg3Gln), rs767413349, NCI-TCGA Cosmic COSV6073, ExAC rs767413349, gnomAD rs767413349, Variant assessed as somatic; moderate impact.
- W6R (p.Trp6Arg), TOPMed rs1761557480, REVEL 0.25, MetaLR 0.11
- S7G (p.Ser7Gly), Ensembl rs2112455622, MetaLR 0.13, MetaSVM -1.04
- Q9H (p.Gln9His), gnomAD rs1406896295, REVEL 0.11, MetaLR 0.18
- C10G (p.Cys10Gly), rs761736517, ClinGen CA3350611, ClinVar RCV003939769, ExAC rs761736517, REVEL 0.16, MetaLR 0.14, Likely benign, PCSK1-related disorder
- C10R (p.Cys10Arg), ExAC rs761736517, TOPMed rs761736517, gnomAD rs761736517, REVEL 0.21, MetaLR 0.14, Likely benign
- C10Y (p.Cys10Tyr), NCI-TCGA TCGA novel, MetaLR 0.13, MetaSVM -1.01, Variant assessed as somatic; moderate impact.
- T11I (p.Thr11Ile), rs774029532, NCI-TCGA Cosmic COSV1002, ExAC rs774029532, gnomAD rs774029532, Variant assessed as somatic; moderate impact.
- A12T (p.Ala12Thr), ExAC rs768156888, gnomAD rs768156888, REVEL 0.15, MetaLR 0.20
- F13L (p.Phe13Leu), rs748979266, ClinGen CA3350608, ClinVar RCV002853294, ExAC rs748979266, REVEL 0.12, MetaLR 0.06, Uncertain significance, not provided
- F13S (p.Phe13Ser), TOPMed rs1173701856, gnomAD rs1173701856, REVEL 0.23, MetaLR 0.18
- V14I (p.Val14Ile), NCI-TCGA Cosmic COSV6073, Variant assessed as somatic; moderate impact.
- L15F (p.Leu15Phe), gnomAD rs1425463282, REVEL 0.08, MetaLR 0.19
- C17* (p.Cys17Ter), rs774807858, NCI-TCGA Cosmic COSV6073, ExAC rs774807858, TOPMed rs774807858, Variant assessed as somatic; high impact.
- A18S (p.Ala18Ser), TOPMed rs1029535554, gnomAD rs1029535554, REVEL 0.09, MetaLR 0.09, Uncertain significance, PCSK1-related disorder
- A18T (p.Ala18Thr), TOPMed rs1029535554, gnomAD rs1029535554, Uncertain significance
- C20W (p.Cys20Trp), TOPMed rs1761556220, MetaLR 0.17, MetaSVM -0.90
- C20Y (p.Cys20Tyr), TOPMed rs1761556331, REVEL 0.10, MetaLR 0.20
- A21E (p.Ala21Glu), Ensembl rs776377807, REVEL 0.17, MetaLR 0.19
- A21V (p.Ala21Val), NCI-TCGA Cosmic COSV6073, MetaLR 0.15, MetaSVM -0.96, Variant assessed as somatic; moderate impact.
- L22M (p.Leu22Met), Ensembl rs901957088, REVEL 0.05, MetaLR 0.08
- L22P (p.Leu22Pro), rs201377789, ClinGen CA3350605, ClinVar RCV001942412, ClinVar RCV003913428, REVEL 0.31, MetaLR 0.13, Uncertain significance, not provided
- S24G (p.Ser24Gly), gnomAD rs1297020758, REVEL 0.13, MetaLR 0.11
- S24I (p.Ser24Ile), TOPMed rs1183154024, gnomAD rs1183154024, REVEL 0.13, MetaLR 0.17, Uncertain significance
- S24N (p.Ser24Asn), rs1183154024, ClinGen CA360486202, ClinVar RCV004500853, TOPMed rs1183154024, REVEL 0.11, MetaLR 0.17, Uncertain significance, Inborn genetic diseases
- K26E (p.Lys26Glu), ExAC rs763973412, TOPMed rs763973412, gnomAD rs763973412, REVEL 0.07, MetaLR 0.13
- K26N (p.Lys26Asn), gnomAD rs1208489419, REVEL 0.06, MetaLR 0.13
- A27T (p.Ala27Thr), Ensembl rs2112455501, REVEL 0.07, MetaLR 0.17
- A27V (p.Ala27Val), rs527304866, ClinGen CA3350602, ClinVar RCV002927610, ClinVar RCV003963428, REVEL 0.05, MetaLR 0.13, Uncertain significance, not provided
- R29S (p.Arg29Ser), ExAC rs747325979, TOPMed rs747325979, gnomAD rs747325979
- Q30K (p.Gln30Lys), TOPMed rs1761554628
- Q30L (p.Gln30Leu), TOPMed rs1761554526, MetaLR 0.14, MetaSVM -0.97
- F31L (p.Phe31Leu), gnomAD rs1225423383, REVEL 0.18, MetaLR 0.10
- V32D (p.Val32Asp), gnomAD rs1402066172, MetaLR 0.06, MetaSVM -1.10
- E34* (p.Glu34Ter), rs778230512, NCI-TCGA Cosmic COSV6073, ExAC rs778230512, gnomAD rs778230512, CADD 37.00, Variant assessed as somatic; high impact.
- E34A (p.Glu34Ala), TOPMed rs1761554037, MetaLR 0.14, MetaSVM -1.04
- A36T (p.Ala36Thr), TOPMed rs937916641, gnomAD rs937916641, REVEL 0.36, MetaLR 0.27, Likely pathogenic, PCSK1-related disorder
- A37V (p.Ala37Val), NCI-TCGA Cosmic COSV6073, MetaLR 0.02, MetaSVM -1.00, Variant assessed as somatic; moderate impact.
- E38K (p.Glu38Lys), rs1049269132, ClinGen CA122939077, ClinVar RCV001879710, ClinVar RCV005465556, REVEL 0.17, MetaLR 0.07, Uncertain significance, Inborn genetic diseases; not provided
- P40H (p.Pro40His), ExAC rs752976241, gnomAD rs752976241, REVEL 0.14, MetaLR 0.10
- P40L (p.Pro40Leu), ExAC rs752976241, gnomAD rs752976241, REVEL 0.15, MetaLR 0.10
- P40S (p.Pro40Ser), Ensembl rs1475159276, REVEL 0.07, MetaLR 0.07
- G41A (p.Gly41Ala), TOPMed rs1302916630, gnomAD rs1302916630, REVEL 0.07, MetaLR 0.07, Uncertain significance, PCSK1-related disorder
- G41R (p.Gly41Arg), rs765217767, ClinGen CA3350597, ClinVar RCV001158139, ClinVar RCV003293909, REVEL 0.23, MetaLR 0.22, Uncertain significance, Inborn genetic diseases; Obesity due to prohormone convertase I deficiency
- G42D (p.Gly42Asp), rs1359353262, ClinGen CA360486083, ClinVar RCV003939801, TOPMed rs1359353262, REVEL 0.22, MetaLR 0.14, Likely pathogenic, PCSK1-related disorder
- G42V (p.Gly42Val), NCI-TCGA Cosmic COSV1002, MetaLR 0.32, MetaSVM -0.24, Variant assessed as somatic; moderate impact.
- P43Q (p.Pro43Gln), TOPMed rs1463744667, gnomAD rs1463744667, REVEL 0.03, MetaLR 0.04, Uncertain significance, Inborn genetic diseases
- A45E (p.Ala45Glu), ExAC rs750350434, TOPMed rs750350434, gnomAD rs750350434, REVEL 0.07, MetaLR 0.03
- A46G (p.Ala46Gly), Ensembl rs1761552233, MetaLR 0.39, MetaSVM -0.04
- S47L (p.Ser47Leu), TOPMed rs1429574639, gnomAD rs1429574639, REVEL 0.02, MetaLR 0.03
- A50G (p.Ala50Gly), TOPMed rs1407263387, gnomAD rs1407263387
- A50S (p.Ala50Ser), Ensembl rs1761552044, REVEL 0.31, MetaLR 0.31
- A50V (p.Ala50Val), TOPMed rs1407263387, gnomAD rs1407263387, MetaLR 0.43, MetaSVM -0.06
- E51K (p.Glu51Lys), ExAC rs761877336, TOPMed rs761877336, gnomAD rs761877336, REVEL 0.06, MetaLR 0.04
- L53V (p.Leu53Val), gnomAD rs1263975971, REVEL 0.08, MetaLR 0.08
- G54S (p.Gly54Ser), TOPMed rs1761551471, REVEL 0.34, MetaLR 0.32
- Y55C (p.Tyr55Cys), ExAC rs763965527, gnomAD rs763965527, REVEL 0.50, MetaLR 0.25
- D56E (p.Asp56Glu), Ensembl rs1761551021
- D56G (p.Asp56Gly), gnomAD rs1228274665, MetaLR 0.08, MetaSVM -1.07
- D56H (p.Asp56His), ExAC rs762502532, gnomAD rs762502532, REVEL 0.06, MetaLR 0.08
- L57F (p.Leu57Phe), TOPMed rs1761550899, gnomAD rs1761550899, REVEL 0.05, MetaLR 0.06
- G59D (p.Gly59Asp), ExAC rs769265374, gnomAD rs769265374, REVEL 0.31, MetaLR 0.23
- G59S (p.Gly59Ser), ExAC rs775280277, TOPMed rs775280277, gnomAD rs775280277, REVEL 0.29, MetaLR 0.23
- Q60E (p.Gln60Glu), TOPMed rs1761550473
- I61F (p.Ile61Phe), gnomAD rs1270940943, REVEL 0.40, MetaLR 0.27
- G62S (p.Gly62Ser), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10022, REVEL 0.13, MetaLR 0.11, Variant assessed as somatic; moderate impact.
- S63L (p.Ser63Leu), cosmic curated COSV10942, ExAC rs756287752, gnomAD rs756287752, REVEL 0.15, MetaLR 0.09
- L64V (p.Leu64Val), Ensembl rs1761416162, REVEL 0.23, MetaLR 0.17
- E65K (p.Glu65Lys), rs868205015, NCI-TCGA Cosmic COSV6073, cosmic curated COSV60737, Ensembl rs868205015, Variant assessed as somatic; moderate impact.
- N66H (p.Asn66His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H67Q (p.His67Gln), Ensembl rs1761415856, REVEL 0.34, MetaLR 0.18
- H67Y (p.His67Tyr), Ensembl rs1761415933, REVEL 0.11, MetaLR 0.04
- Y68H (p.Tyr68His), TOPMed rs1761415763
- F70L (p.Phe70Leu), NCI-TCGA Cosmic COSV6073, cosmic curated COSV60736, REVEL 0.13, MetaLR 0.12, Variant assessed as somatic; moderate impact.
- F70S (p.Phe70Ser), Ensembl rs867524772, MetaLR 0.33, MetaSVM -0.13
- K71Q (p.Lys71Gln), TOPMed rs1284647524, gnomAD rs1284647524, REVEL 0.03, MetaLR 0.05
- H72Y (p.His72Tyr), gnomAD rs1206696074, REVEL 0.20, MetaLR 0.13
- P76S (p.Pro76Ser), rs371368465, ClinGen CA3350555, ClinVar RCV003393083, ESP rs371368465, REVEL 0.18, MetaLR 0.07, Uncertain significance, PCSK1-related disorder
- R78K (p.Arg78Lys), rs1761415135, ClinGen CA360485250, cosmic curated COSV60737, ClinVar RCV003412255, REVEL 0.25, MetaLR 0.14, Uncertain significance, PCSK1-related disorder
- R78S (p.Arg78Ser), ESP rs148354360, ExAC rs148354360, TOPMed rs148354360, gnomAD rs148354360, REVEL 0.31, MetaLR 0.22, Uncertain significance, PCSK1-related disorder
- S79C (p.Ser79Cys), rs1339347581, ClinGen CA360485242, ClinVar RCV003414556, TOPMed rs1339347581, REVEL 0.32, MetaLR 0.27, Uncertain significance, PCSK1-related disorder
- S79Y (p.Ser79Tyr), TOPMed rs1339347581, gnomAD rs1339347581, MetaLR 0.25, MetaSVM -0.48, Uncertain significance
- R80* (p.Arg80Ter), rs765019354, ClinGen CA360485240, ClinVar RCV001290206, ExAC rs765019354, CADD 37.00, Pathogenic
- R80G (p.Arg80Gly), ExAC rs765019354, TOPMed rs765019354, gnomAD rs765019354, REVEL 0.21, MetaLR 0.12, Pathogenic
- R80L (p.Arg80Leu), 1000Genomes rs1799904, ExAC rs1799904, TOPMed rs1799904, gnomAD rs1799904, REVEL 0.07, MetaLR 0.07, Benign
- R80Q (p.Arg80Gln), rs1799904, ClinGen CA3350550, cosmic curated COSV10942, ClinVar RCV001822203, REVEL 0.21, MetaLR 0.06, Benign/Likely benign, not specified; not provided
- R81M (p.Arg81Met), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10022, MetaLR 0.26, MetaSVM -0.52, Variant assessed as somatic; moderate impact.
- R81S (p.Arg81Ser), gnomAD rs1398624849, REVEL 0.24, MetaLR 0.11
- S82C (p.Ser82Cys), ExAC rs760269702, gnomAD rs760269702, REVEL 0.27, MetaLR 0.20
- S82G (p.Ser82Gly), ExAC rs760269702, gnomAD rs760269702, REVEL 0.06, MetaLR 0.10
- S82T (p.Ser82Thr), gnomAD rs1319360811, REVEL 0.15, MetaLR 0.12
- F84S (p.Phe84Ser), NCI-TCGA TCGA novel, MetaLR 0.04, MetaSVM -0.98, Variant assessed as somatic; moderate impact.
- I86L (p.Ile86Leu), gnomAD rs1400328008, MetaLR 0.05, MetaSVM -1.07
- I86V (p.Ile86Val), gnomAD rs1400328008, REVEL 0.04, MetaLR 0.05
- T87S (p.Thr87Ser), NCI-TCGA Cosmic COSV6073, cosmic curated COSV60735, MetaLR 0.13, MetaSVM -1.06, Variant assessed as somatic; moderate impact.
- K88N (p.Lys88Asn), NCI-TCGA Cosmic COSV6073, MetaLR 0.09, MetaSVM -1.10, Variant assessed as somatic; moderate impact.
- K88R (p.Lys88Arg), cosmic curated COSV60738, TOPMed rs1422794750, gnomAD rs1422794750, REVEL 0.03, MetaLR 0.06
- R89I (p.Arg89Ile), NCI-TCGA Cosmic COSV6073, cosmic curated COSV60733, MetaLR 0.16, MetaSVM -0.91, Variant assessed as somatic; moderate impact.
- L90S (p.Leu90Ser), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10022, REVEL 0.75, MetaLR 0.50, Variant assessed as somatic; moderate impact.
- S91P (p.Ser91Pro), TOPMed rs1431453437, gnomAD rs1431453437, REVEL 0.17, MetaLR 0.11
- D93E (p.Asp93Glu), ExAC rs762255140, gnomAD rs762255140, REVEL 0.15, MetaLR 0.08
- D93G (p.Asp93Gly), gnomAD rs1475015594, REVEL 0.38, MetaLR 0.14
- D94G (p.Asp94Gly), rs1195026964, ClinGen CA360485074, ClinVar RCV003959250, TOPMed rs1195026964, REVEL 0.06, MetaLR 0.07, Uncertain significance, PCSK1-related disorder
- D94N (p.Asp94Asn), rs1761413119, ClinGen CA360485078, ClinVar RCV002275437, Ensembl rs1761413119, REVEL 0.04, MetaLR 0.07, Uncertain significance, not provided
- R95C (p.Arg95Cys), rs1439220661, cosmic curated COSV10459, TOPMed rs1439220661, gnomAD rs1439220661, REVEL 0.34, MetaLR 0.19, Variant assessed as somatic; moderate impact.
- R95H (p.Arg95His), rs769203665, ClinGen CA3350543, ClinVar RCV000364590, ExAC rs769203665, REVEL 0.23, MetaLR 0.17, Uncertain significance, Obesity due to prohormone convertase I deficiency
- V96A (p.Val96Ala), ExAC rs763461063, TOPMed rs763461063, gnomAD rs763461063, REVEL 0.66, MetaLR 0.44
- I97L (p.Ile97Leu), Ensembl rs1580768233, MetaLR 0.03, MetaSVM -1.04
- I97T (p.Ile97Thr), cosmic curated COSV60737, gnomAD rs1385225623, REVEL 0.06, MetaLR 0.03
- W98R (p.Trp98Arg), rs1246742230, ClinGen CA360484831, ClinVar RCV003405981, TOPMed rs1246742230, REVEL 0.63, MetaLR 0.26, Uncertain significance, PCSK1-related disorder
- A99P (p.Ala99Pro), TOPMed rs1282004766, gnomAD rs1282004766, REVEL 0.49, MetaLR 0.29
- A99V (p.Ala99Val), rs776019151, ClinGen CA3350523, ClinVar RCV001979145, ClinVar RCV004746535, REVEL 0.24, MetaLR 0.08, Uncertain significance, not provided
- E100D (p.Glu100Asp), TOPMed rs1761292564
- E100G (p.Glu100Gly), Ensembl rs1761292640
- E100Q (p.Glu100Gln), NCI-TCGA Cosmic COSV6073, cosmic curated COSV60735, MetaLR 0.09, MetaSVM -1.00, Variant assessed as somatic; moderate impact.
- Q102* (p.Gln102Ter), ExAC rs746083941, TOPMed rs746083941, gnomAD rs746083941, CADD 42.00
- Q102E (p.Gln102Glu), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10022, NCI-TCGA Cosmic COSV6073, Variant assessed as somatic; moderate impact.
- Y103N (p.Tyr103Asn), gnomAD rs1330986908, REVEL 0.23, MetaLR 0.08
- E104K (p.Glu104Lys), cosmic curated COSV10513, gnomAD rs1403500864
- E106K (p.Glu106Lys), gnomAD rs1364933057, REVEL 0.10, MetaLR 0.07
- E106Q (p.Glu106Gln), NCI-TCGA Cosmic COSV6073, cosmic curated COSV60734, MetaLR 0.13, MetaSVM -0.99, Variant assessed as somatic; moderate impact.
- R107K (p.Arg107Lys), ExAC rs776713450, gnomAD rs776713450, REVEL 0.44, MetaLR 0.63
- S108T (p.Ser108Thr), rs1761291996, ClinGen CA360484753, ClinVar RCV003295057, Ensembl rs1761291996, REVEL 0.03, MetaLR 0.08, Likely benign, Inborn genetic diseases
- K109T (p.Lys109Thr), NCI-TCGA Cosmic COSV6073, cosmic curated COSV60734, gnomAD rs1761291845, MetaLR 0.62, MetaSVM 0.42, Variant assessed as somatic; moderate impact.
- R110C (p.Arg110Cys), ExAC rs774036542, TOPMed rs774036542, gnomAD rs774036542, REVEL 0.70, MetaLR 0.71, Uncertain significance, PCSK1-related disorder
- R110H (p.Arg110His), cosmic curated COSV60735, ExAC rs748072514, TOPMed rs748072514, gnomAD rs748072514, REVEL 0.67, MetaLR 0.64, Uncertain significance, PCSK1-related disorder
- S111* (p.Ser111Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- S111L (p.Ser111Leu), TOPMed rs1761291503, MetaLR 0.14, MetaSVM -0.91
- A112D (p.Ala112Asp), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A112T (p.Ala112Thr), rs1028311261, ClinGen CA122932662, ClinVar RCV001699928, TOPMed rs1028311261, REVEL 0.01, MetaLR 0.17, Likely benign, not provided
- A112V (p.Ala112Val), ExAC rs778861116, TOPMed rs778861116, gnomAD rs778861116, MetaLR 0.08, MetaSVM -1.02
- L113I (p.Leu113Ile), ExAC rs754742271, TOPMed rs754742271, gnomAD rs754742271, REVEL 0.04, MetaLR 0.12
- D115A (p.Asp115Ala), 1000Genomes rs200893367, ExAC rs200893367, gnomAD rs200893367, REVEL 0.21, MetaLR 0.24
- A117T (p.Ala117Thr), TOPMed rs1761290460
- A117V (p.Ala117Val), gnomAD rs1761290355, REVEL 0.08, MetaLR 0.23
- N119H (p.Asn119His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N122S (p.Asn122Ser), rs1237338413, ClinGen CA360484665, ClinVar RCV003414398, TOPMed rs1237338413, REVEL 0.42, MetaLR 0.42, Uncertain significance, PCSK1-related disorder
- D123N (p.Asp123Asn), NCI-TCGA Cosmic COSV6073, cosmic curated COSV60736, MetaLR 0.76, MetaSVM 0.55, Variant assessed as somatic; moderate impact.
- P124L (p.Pro124Leu), Ensembl rs1561376921, REVEL 0.84, MetaLR 0.77
- M125I (p.Met125Ile), rs146545244, 1000Genomes rs146545244, ESP rs146545244, ExAC rs146545244, REVEL 0.33, MetaLR 0.34, Uncertain significance, Obesity due to prohormone convertase I deficiency; not provided
- M125K (p.Met125Lys), rs369663700, ClinGen CA3350510, ClinVar RCV003949364, ESP rs369663700, REVEL 0.48, MetaLR 0.23, Uncertain significance, PCSK1-related disorder
- W126* (p.Trp126Ter), Ensembl rs2112445282, NCI-TCGA Cosmic COSV6073, cosmic curated COSV60737, Variant assessed as somatic; high impact.
- N127I (p.Asn127Ile), rs574780528, ClinGen CA3350508, ClinVar RCV003901650, 1000Genomes rs574780528, REVEL 0.43, MetaLR 0.40, Likely benign, PCSK1-related disorder
- Q128* (p.Gln128Ter), NCI-TCGA Cosmic COSV6073, cosmic curated COSV60734, CADD 41.00, Variant assessed as somatic; high impact.
- W130L (p.Trp130Leu), TOPMed rs1434467255, gnomAD rs1434467255, REVEL 0.90, MetaLR 0.82
- W130S (p.Trp130Ser), TOPMed rs1434467255, gnomAD rs1434467255, REVEL 0.88, MetaLR 0.82
- L132F (p.Leu132Phe), ExAC rs763585508, gnomAD rs763585508, REVEL 0.79, MetaLR 0.84
- T135I (p.Thr135Ile), cosmic curated COSV60736, ESP rs376953881, ExAC rs376953881, TOPMed rs376953881, REVEL 0.63, MetaLR 0.68
- M137L (p.Met137Leu), ESP rs372023054, TOPMed rs372023054, gnomAD rs372023054, REVEL 0.12, MetaLR 0.30
- T138K (p.Thr138Lys), ExAC rs759857993, TOPMed rs759857993, gnomAD rs759857993, REVEL 0.20, MetaLR 0.36, Likely benign
- T138M (p.Thr138Met), rs759857993, ClinGen CA3350485, ClinVar RCV003427866, ClinVar RCV003883992, REVEL 0.26, MetaLR 0.49, Conflicting interpretations, PCSK1-related disorder; not provided
- A140S (p.Ala140Ser), gnomAD rs1177991204
- A140T (p.Ala140Thr), rs1177991204, gnomAD rs1177991204, Variant assessed as somatic; moderate impact.
- A140V (p.Ala140Val), ExAC rs754068131, gnomAD rs754068131, REVEL 0.08, MetaLR 0.15
- L141Q (p.Leu141Gln), gnomAD rs1486438351, REVEL 0.39, MetaLR 0.27
- L141V (p.Leu141Val), 1000Genomes rs563418997, ExAC rs563418997, gnomAD rs563418997, REVEL 0.24, MetaLR 0.30
- L144M (p.Leu144Met), TOPMed rs945585569
- D145N (p.Asp145Asn), ExAC rs773206783, gnomAD rs773206783, REVEL 0.73, MetaLR 0.74
- L146F (p.Leu146Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L146I (p.Leu146Ile), Ensembl rs752094127
- L146R (p.Leu146Arg), NCI-TCGA Cosmic COSV1002, cosmic curated COSV10022, Variant assessed as somatic; moderate impact.
- V148M (p.Val148Met), Ensembl rs964063462
- I149T (p.Ile149Thr), ExAC rs772150249, gnomAD rs772150249, REVEL 0.35, MetaLR 0.32
- P150L (p.Pro150Leu), gnomAD rs1225474199, REVEL 0.69, MetaLR 0.67
- P150T (p.Pro150Thr), gnomAD rs1263789931
- W152L (p.Trp152Leu), Ensembl rs868424536, MetaLR 0.79, MetaSVM 0.71
- K154N (p.Lys154Asn), ESP rs145659863, ExAC rs145659863, TOPMed rs145659863, gnomAD rs145659863, REVEL 0.22, MetaLR 0.37, Uncertain significance, PCSK1-related disorder
- G155D (p.Gly155Asp), gnomAD rs1363728113, REVEL 0.88, MetaLR 0.79
- G155S (p.Gly155Ser), TOPMed rs1382566997, gnomAD rs1382566997, REVEL 0.93, MetaLR 0.79, Uncertain significance, Inborn genetic diseases
- I156T (p.Ile156Thr), rs368303692, ClinGen CA3350478, ClinVar RCV003392758, ESP rs368303692, REVEL 0.81, MetaLR 0.61, Uncertain significance, PCSK1-related disorder
- T157K (p.Thr157Lys), ESP rs200462856, ExAC rs200462856, TOPMed rs200462856, gnomAD rs200462856, MetaLR 0.68, MetaSVM 0.47, Likely pathogenic
- T157M (p.Thr157Met), rs200462856, ClinGen CA3350477, ClinVar RCV001822262, ClinVar RCV003941147, REVEL 0.82, MetaLR 0.81, Uncertain significance, not specified
- T157S (p.Thr157Ser), gnomAD rs1406395982, REVEL 0.61, MetaLR 0.63
- G158A (p.Gly158Ala), TOPMed rs1490377137, gnomAD rs1490377137, REVEL 0.85, MetaLR 0.87
- G160* (p.Gly160Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- G160V (p.Gly160Val), TOPMed rs1761185567, MetaLR 0.86, MetaSVM 0.91
Public PCSK1 analysis runs
- PCSK1 analysis run — PCSK1 (1,097 variants) — completed 2026-08-19