PKLR (Pyruvate kinase PKLR) variants and mutations
PKLR (also known as Pyruvate kinase PKLR) is a human protein-coding gene encoding a pyruvate kinase protein. It catalyzes the final ATP-generating step of glycolysis in red blood cells and liver. Biallelic loss-of-function variants cause pyruvate kinase deficiency, leading to chronic nonspherocytic hemolytic anemia because erythrocytes cannot maintain adequate ATP production. This analysis covers 1,019 PKLR variants and mutations. Of these, 75% have computational variant effect predictions. Disease context includes pyruvate kinase deficiency of red cells, Hemolytic anemia due to red cell pyruvate kinase deficiency, and pyruvate kinase hyperactivity. Example PKLR variants include S2*, S2L, and S2W.
Variant analysis overview
- Gene: PKLR
- Protein: Pyruvate kinase PKLR
- UniProt accession: P30613
- Organism: Homo sapiens
- Variants analyzed: 1019
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 813 unspecified-consequence records; 4 stop lost; 1 stop retained variant; 96 synonymous variants; 87 missense variants; 11 frameshift variants; 4 in-frame deletions; 2 stop-gained variants; 2 splice-region variants; 3 substitution
- Prediction scores: 765 variants have prediction scores (75% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: pyruvate kinase deficiency of red cells, Hemolytic anemia due to red cell pyruvate kinase deficiency, pyruvate kinase hyperactivity, congenital anemia, sickle cell disease, severe acute respiratory syndrome, familial hemolytic anemia, Alpha-thalassemia, Beta-thalassemia, beta thalassemia, thalassemia, gout.
Protein structure and variant hotspots
- Protein features: 18 binding sites; 5 post-translational modification sites.
- PTM context: 11 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 PKLR variants
Examples include S2*, S2L, S2W, Q4H, I7K, I7T, S8*, S8P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2* (p.Ser2Ter), ExAC rs774176341, TOPMed rs774176341, gnomAD rs774176341, CADD 33.00
- S2L (p.Ser2Leu), ExAC rs774176341, TOPMed rs774176341, gnomAD rs774176341, NCI-TCGA Cosmic COSV6136, REVEL 0.55, CADD 21.40, Uncertain significance, Pyruvate kinase deficiency of red cells
- S2W (p.Ser2Trp), ExAC rs774176341, TOPMed rs774176341, gnomAD rs774176341, REVEL 0.54, CADD 21.40
- Q4H (p.Gln4His), Ensembl rs758112712
- I7K (p.Ile7Lys), ExAC rs762490269, gnomAD rs762490269, REVEL 0.32, CADD 1.81, Uncertain significance
- I7T (p.Ile7Thr), rs762490269, ExAC rs762490269, gnomAD rs762490269, ClinGen CA1144514, REVEL 0.21, CADD 0.13, Uncertain significance, not provided
- S8* (p.Ser8Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- S8P (p.Ser8Pro), TOPMed rs1647981030, gnomAD rs1647981030, REVEL 0.30, CADD 4.98
- S9P (p.Ser9Pro), NCI-TCGA TCGA novel, REVEL 0.29, CADD 2.41, Variant assessed as somatic; moderate impact.
- L12V (p.Leu12Val), Ensembl rs1647980781
- R13Q (p.Arg13Gln), rs769174570, ClinGen CA1144512, ClinVar RCV003259651, ClinVar RCV004790514, REVEL 0.34, CADD 13.30, Uncertain significance, not provided; Inborn genetic diseases
- R13W (p.Arg13Trp), ExAC rs772818969, TOPMed rs772818969, gnomAD rs772818969, REVEL 0.32, CADD 10.00, Uncertain significance, not provided
- W15* (p.Trp15Ter), Ensembl rs750812851
- W15R (p.Trp15Arg), ExAC rs748703432, TOPMed rs748703432, gnomAD rs748703432, REVEL 0.44, CADD 7.55
- S17C (p.Ser17Cys), TOPMed rs1442131020, gnomAD rs1442131020, REVEL 0.51, AlphaMissense 0.11
- S17F (p.Ser17Phe), rs1442131020, TOPMed rs1442131020, gnomAD rs1442131020, NCI-TCGA Cosmic COSV6136, AlphaMissense 0.11, MetaLR 0.91, Variant assessed as somatic; moderate impact.
- S17Y (p.Ser17Tyr), TOPMed rs1442131020, gnomAD rs1442131020, REVEL 0.46, AlphaMissense 0.11
- K18E (p.Lys18Glu), ExAC rs781610938, gnomAD rs781610938
- S19C (p.Ser19Cys), ExAC rs769038526, gnomAD rs769038526
- S19Y (p.Ser19Tyr), ExAC rs769038526, gnomAD rs769038526
- Q20R (p.Gln20Arg), TOPMed rs200357340, gnomAD rs200357340, REVEL 0.52, CADD 22.40
- R21K (p.Arg21Lys), TOPMed rs1278895712, gnomAD rs1278895712, REVEL 0.35, CADD 6.07
- D22N (p.Asp22Asn), gnomAD rs1201759277
- D22V (p.Asp22Val), Ensembl rs1647979024, REVEL 0.67, CADD 24.50, Uncertain significance, not provided
- L23* (p.Leu23Ter), rs2525345893, ClinGen CA342759168, ClinVar RCV003990643, Likely pathogenic
- L23I (p.Leu23Ile), TOPMed rs1553231692
- A24E (p.Ala24Glu), NCI-TCGA Cosmic COSV6136, Variant assessed as somatic; moderate impact.
- A24T (p.Ala24Thr), rs754783713, ClinGen CA30910008, ClinVar RCV003886905, TOPMed rs754783713, REVEL 0.24, CADD 13.00, Uncertain significance, not provided
- A24V (p.Ala24Val), TOPMed rs1394682499, gnomAD rs1394682499, REVEL 0.28, CADD 12.60
- K25E (p.Lys25Glu), TOPMed rs1647978536
- S26C (p.Ser26Cys), ExAC rs747323509, gnomAD rs747323509, REVEL 0.48, CADD 23.80
- I27V (p.Ile27Val), Ensembl rs1647978191, REVEL 0.22, CADD 0.30
- L28P (p.Leu28Pro), ExAC rs780370877, gnomAD rs780370877, REVEL 0.63, CADD 24.80
- I29T (p.Ile29Thr), rs142735355, ESP rs142735355, ExAC rs142735355, TOPMed rs142735355, REVEL 0.31, CADD 2.66, Uncertain significance, not provided
- I29V (p.Ile29Val), Ensembl rs1647977935, REVEL 0.29, CADD 6.24
- G30E (p.Gly30Glu), Ensembl rs771523060
- A31D (p.Ala31Asp), ESP rs150077703, ExAC rs150077703, TOPMed rs150077703, gnomAD rs150077703, REVEL 0.63, CADD 24.60, Uncertain significance
- A31P (p.Ala31Pro), TOPMed rs1446138836, gnomAD rs1446138836, REVEL 0.61, CADD 25.20
- A31T (p.Ala31Thr), TOPMed rs1446138836, gnomAD rs1446138836, REVEL 0.52, CADD 25.20
- A31V (p.Ala31Val), rs150077703, ClinGen CA1144505, ClinVar RCV001096025, ClinVar RCV001508890, REVEL 0.55, CADD 24.80, Conflicting interpretations, not provided; Pyruvate kinase deficiency of red cells
- P32A (p.Pro32Ala), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- P32L (p.Pro32Leu), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- G33R (p.Gly33Arg), TOPMed rs1647977007, gnomAD rs1647977007, REVEL 0.50, CADD 20.70
- G34V (p.Gly34Val), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, Variant assessed as somatic; moderate impact.
- P35S (p.Pro35Ser), cosmic curated COSV10071, gnomAD rs1173752341
- A36G (p.Ala36Gly), ExAC rs770019694, TOPMed rs770019694, gnomAD rs770019694, REVEL 0.68, CADD 19.60
- A36V (p.Ala36Val), ExAC rs770019694, TOPMed rs770019694, gnomAD rs770019694, REVEL 0.38, CADD 21.50
- G37E (p.Gly37Glu), rs118204087, ClinGen CA115036, ClinVar RCV000001576, UniProt VAR 011435, REVEL 0.64, CADD 19.70, Affects, Pyruvate kinase hyperactivity
- G37V (p.Gly37Val), ExAC rs118204087, gnomAD rs118204087, REVEL 0.65, CADD 22.50
- R40L (p.Arg40Leu), ExAC rs745811076, TOPMed rs745811076, gnomAD rs745811076, REVEL 0.48, CADD 19.60, Uncertain significance, in CNSHA2
- R40P (p.Arg40Pro), ExAC rs745811076, TOPMed rs745811076, gnomAD rs745811076, Uncertain significance, in CNSHA2
- R40Q (p.Arg40Gln), rs745811076, ExAC rs745811076, TOPMed rs745811076, gnomAD rs745811076, REVEL 0.35, CADD 16.80, Uncertain significance, not provided
- R40W (p.Arg40Trp), rs1484388413, UniProt VAR 058467, gnomAD rs1484388413, REVEL 0.58, CADD 22.40, Uncertain significance, not provided
- R41L (p.Arg41Leu), 1000Genomes rs374805791, ExAC rs374805791, TOPMed rs374805791, gnomAD rs374805791, REVEL 0.50, CADD 20.10, Likely benign
- R41Q (p.Arg41Gln), rs374805791, 1000Genomes rs374805791, ExAC rs374805791, TOPMed rs374805791, REVEL 0.41, CADD 21.10, Uncertain significance, Pyruvate kinase deficiency of red cells
- R41W (p.Arg41Trp), rs375189218, ClinGen CA1144441, ClinVar RCV000283593, ClinVar RCV003137904, REVEL 0.54, CADD 23.00, Uncertain significance, not provided; Pyruvate kinase deficiency of red cells
- A42G (p.Ala42Gly), Ensembl rs1553231550
- S43T (p.Ser43Thr), NCI-TCGA Cosmic COSV6136, cosmic curated COSV61361, Variant assessed as somatic; moderate impact.
- V44E (p.Val44Glu), Ensembl rs753415917
- V44M (p.Val44Met), gnomAD rs924210755, REVEL 0.34, CADD 19.40
- Q46K (p.Gln46Lys), gnomAD rs1305717947
- Q49* (p.Gln49Ter), gnomAD rs1380918810, CADD 36.00
- Q49H (p.Gln49His), TOPMed rs1647912559, REVEL 0.41, CADD 18.30, Uncertain significance, Inborn genetic diseases
- E50K (p.Glu50Lys), ExAC rs752199380, gnomAD rs752199380, cosmic curated COSV61361, REVEL 0.58, CADD 26.00, Uncertain significance, not provided
- L51P (p.Leu51Pro), TOPMed rs1185596611
- G52C (p.Gly52Cys), ExAC rs760029571, gnomAD rs760029571, REVEL 0.66, CADD 25.40
- G52D (p.Gly52Asp), ExAC rs752093404, gnomAD rs752093404
- T53I (p.Thr53Ile), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, REVEL 0.38, CADD 21.30, Variant assessed as somatic; moderate impact.
- T53S (p.Thr53Ser), Ensembl rs760443294
- A54T (p.Ala54Thr), Ensembl rs753089348, REVEL 0.29, CADD 14.90
- A54V (p.Ala54Val), Ensembl rs1374868491
- F56Y (p.Phe56Tyr), Ensembl rs746308116
- Q57* (p.Gln57Ter), rs772567442, ClinGen CA30909235, ClinVar RCV001000991, TOPMed rs772567442, CADD 36.00, Pathogenic
- A63G (p.Ala63Gly), rs886045353, ClinGen CA10608274, ClinVar RCV000342304, ClinVar RCV003133211, REVEL 0.67, CADD 28.20, Uncertain significance, not provided; Pyruvate kinase deficiency of red cells
- A63T (p.Ala63Thr), rs1165604977, TOPMed rs1165604977, gnomAD rs1165604977, ClinGen CA342758477, REVEL 0.65, CADD 26.20, Uncertain significance, not provided
- M65L (p.Met65Leu), ExAC rs773589949, TOPMed rs773589949, gnomAD rs773589949
- M65T (p.Met65Thr), TOPMed rs1187424402, gnomAD rs1187424402
- M65V (p.Met65Val), ExAC rs773589949, TOPMed rs773589949, gnomAD rs773589949
- T68N (p.Thr68Asn), TOPMed rs1647908455, REVEL 0.54, CADD 22.40
- L70P (p.Leu70Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E71V (p.Glu71Val), cosmic curated COSV10743, Ensembl rs754696137
- L73F (p.Leu73Phe), rs200791251, ClinGen CA1144427, ClinVar RCV001508889, ExAC rs200791251, REVEL 0.52, CADD 22.50, Uncertain significance, not provided
- L73H (p.Leu73His), ESP rs140571200, TOPMed rs140571200, gnomAD rs140571200, REVEL 0.84, CADD 26.30, Uncertain significance, not provided
- L73P (p.Leu73Pro), ESP rs140571200, TOPMed rs140571200, gnomAD rs140571200, UniProt VAR 058469, REVEL 0.92, CADD 27.90, Pathogenic, in CNSHA2
- C74S (p.Cys74Ser), rs1394809863, TOPMed rs1394809863, gnomAD rs1394809863, ClinGen CA342758357, REVEL 0.78, CADD 23.40, Uncertain significance, not provided
- L75P (p.Leu75Pro), rs2148218886, ClinGen CA342758341, ClinVar RCV001729977, Ensembl rs2148218886, AlphaMissense 0.93, MetaLR 0.94, Likely pathogenic, Pyruvate kinase deficiency of red cells
- L76M (p.Leu76Met), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, Variant assessed as somatic; moderate impact.
- L76P (p.Leu76Pro), rs1331269086, ClinGen CA342758328, NCI-TCGA Cosmic COSV1007, REVEL 0.88, CADD 25.40, Uncertain significance, Pyruvate kinase deficiency of red cells
- L76Q (p.Leu76Gln), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, NCI-TCGA Cosmic COSV6136, Variant assessed as somatic; moderate impact.
- L76R (p.Leu76Arg), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, NCI-TCGA Cosmic COSV6136, Variant assessed as somatic; moderate impact.
- S80P (p.Ser80Pro), UniProt VAR 011436, Pathogenic, in CNSHA2
- S80T (p.Ser80Thr), Ensembl rs766051969
- E81K (p.Glu81Lys), ESP rs139707114, ExAC rs139707114, TOPMed rs139707114, gnomAD rs139707114, REVEL 0.54, CADD 17.10, Uncertain significance, not provided
- P82A (p.Pro82Ala), ESP rs151005140, ExAC rs151005140, TOPMed rs151005140, gnomAD rs151005140, REVEL 0.73, CADD 22.80
- P82L (p.Pro82Leu), cosmic curated COSV10523, gnomAD rs1291071651, REVEL 0.79, CADD 24.90, Uncertain significance, Inborn genetic diseases
- V83A (p.Val83Ala), Ensembl rs754785851
- V83M (p.Val83Met), rs368492204, ESP rs368492204, ExAC rs368492204, TOPMed rs368492204, REVEL 0.32, CADD 7.94, Uncertain significance, Inborn genetic diseases; not provided
- A85T (p.Ala85Thr), gnomAD rs1273516896, REVEL 0.41, CADD 14.70
- R86C (p.Arg86Cys), ExAC rs752391774, TOPMed rs752391774, gnomAD rs752391774, cosmic curated COSV10967, REVEL 0.87, CADD 24.70, Uncertain significance, in CNSHA2
- R86G (p.Arg86Gly), rs752391774, ClinGen CA1144419, ClinVar RCV001508888, ExAC rs752391774, REVEL 0.90, CADD 23.90, Uncertain significance, not provided
- R86H (p.Arg86His), rs375471342, ClinGen CA1144418, ClinVar RCV003131977, ESP rs375471342, REVEL 0.89, CADD 24.60, Conflicting interpretations, not provided
- R86P (p.Arg86Pro), UniProt VAR 011437, Pathogenic, in CNSHA2
- S87C (p.Ser87Cys), ExAC rs754454017, TOPMed rs754454017, gnomAD rs754454017, REVEL 0.66, CADD 23.60
- S87G (p.Ser87Gly), ExAC rs754454017, TOPMed rs754454017, gnomAD rs754454017, REVEL 0.42, CADD 20.10
- S87N (p.Ser87Asn), rs2525337015, ClinGen CA342758148, ClinVar RCV003142681, REVEL 0.39, CADD 15.70, Uncertain significance, not provided
- T88S (p.Thr88Ser), Ensembl rs1553231499
- I90N (p.Ile90Asn), TOPMed rs1647900493, UniProt VAR 011438, REVEL 0.95, CADD 28.50, Pathogenic, in CNSHA2
- I91T (p.Ile91Thr), rs752037743, ClinGen CA1144416, ClinVar RCV002005495, ExAC rs752037743, REVEL 0.96, CADD 27.00, Uncertain significance, not provided
- I91V (p.Ile91Val), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, Variant assessed as somatic; moderate impact.
- A92D (p.Ala92Asp), rs2525336892, ClinGen CA342758037, ClinVar RCV002718255, Uncertain significance, Inborn genetic diseases
- G95R (p.Gly95Arg), rs750857114, ExAC rs750857114, TOPMed rs750857114, gnomAD rs750857114, REVEL 0.98, CADD 34.00, Pathogenic, in CNSHA2
- G95W (p.Gly95Trp), ExAC rs750857114, TOPMed rs750857114, gnomAD rs750857114, REVEL 0.95, CADD 34.00
- P96S (p.Pro96Ser), rs1474390898, TOPMed rs1474390898, gnomAD rs1474390898, REVEL 0.94, CADD 25.70, Variant assessed as somatic; moderate impact.
- S98T (p.Ser98Thr), rs1302535902, ClinGen CA342756546, ClinVar RCV002003104, ClinVar RCV005382322, REVEL 0.70, CADD 21.80, Uncertain significance, not provided; Inborn genetic diseases
- R99C (p.Arg99Cys), ESP rs148636159, ExAC rs148636159, gnomAD rs148636159, REVEL 0.74, CADD 26.30
- R99H (p.Arg99His), cosmic curated COSV61362, 1000Genomes rs534895384, ExAC rs534895384, gnomAD rs534895384, REVEL 0.62, CADD 23.70
- S100T (p.Ser100Thr), ExAC rs762661462, gnomAD rs762661462, REVEL 0.71, CADD 22.70
- V101A (p.Val101Ala), rs1572057758, ClinGen CA342756349, ClinVar RCV001001145, Ensembl rs1572057758, REVEL 0.84, CADD 30.00, Uncertain significance, not specified
- V101L (p.Val101Leu), ESP rs143984223, ExAC rs143984223, TOPMed rs143984223, gnomAD rs143984223, REVEL 0.67, CADD 22.90, Uncertain significance, not provided
- V101M (p.Val101Met), ESP rs143984223, ExAC rs143984223, TOPMed rs143984223, gnomAD rs143984223, REVEL 0.83, CADD 26.90
- E102G (p.Glu102Gly), TOPMed rs1647552348, REVEL 0.69, CADD 27.00
- E102K (p.Glu102Lys), NCI-TCGA TCGA novel, REVEL 0.75, CADD 25.10, Variant assessed as somatic; moderate impact.
- R103C (p.Arg103Cys), cosmic curated COSV61360, ExAC rs779765565, TOPMed rs779765565, gnomAD rs779765565, REVEL 0.57, CADD 32.00
- R103G (p.Arg103Gly), ExAC rs779765565, TOPMed rs779765565, gnomAD rs779765565, REVEL 0.54, CADD 24.30
- R103H (p.Arg103His), ESP rs371471086
- R103S (p.Arg103Ser), ExAC rs779765565, TOPMed rs779765565, gnomAD rs779765565, cosmic curated COSV61360, REVEL 0.44, CADD 23.20, Uncertain significance, Inborn genetic diseases
- K105R (p.Lys105Arg), TOPMed rs1647551634, REVEL 0.44, CADD 22.60
- E106Q (p.Glu106Gln), gnomAD rs1647551316, REVEL 0.45, CADD 23.10
- M107I (p.Met107Ile), TOPMed rs1647550981, gnomAD rs1647550981, REVEL 0.90, CADD 26.60
- M107T (p.Met107Thr), rs2525304199, ClinGen CA342756264, ClinVar RCV003562296, UniProt VAR 004028, REVEL 0.95, CADD 27.30, Uncertain significance, not provided
- I108V (p.Ile108Val), TOPMed rs1647550818, gnomAD rs1647550818, REVEL 0.56, CADD 23.10
- K109E (p.Lys109Glu), gnomAD rs1159724535, REVEL 0.47, CADD 22.80
- A110D (p.Ala110Asp), Ensembl rs1553230926
- A110P (p.Ala110Pro), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A110T (p.Ala110Thr), rs1557960823, Ensembl rs1557960823, REVEL 0.59, CADD 22.80, Variant assessed as somatic; moderate impact.
- A110V (p.Ala110Val), NCI-TCGA Cosmic COSV6136, cosmic curated COSV61361, Variant assessed as somatic; moderate impact.
- G111E (p.Gly111Glu), TOPMed rs1325130058, gnomAD rs1325130058, cosmic curated COSV10648, REVEL 0.94, CADD 27.40
- G111R (p.Gly111Arg), rs918627824, ClinGen CA30904892, ClinVar RCV000625798, ClinVar RCV003488737, REVEL 0.96, CADD 29.40, Pathogenic/Likely pathogenic, not provided; Pyruvate kinase deficiency of red cells
- M112I (p.Met112Ile), rs1553230922, NCI-TCGA Cosmic COSV6136, Ensembl rs1553230922, cosmic curated COSV61360, AlphaMissense 0.77, MetaLR 0.99, Variant assessed as somatic; moderate impact.
- M112L (p.Met112Leu), ExAC rs746377052, TOPMed rs746377052, gnomAD rs746377052, REVEL 0.84, CADD 25.50
- M112V (p.Met112Val), ExAC rs746377052, TOPMed rs746377052, gnomAD rs746377052, REVEL 0.87, CADD 25.10
- N113S (p.Asn113Ser), TOPMed rs1347580980
- I114T (p.Ile114Thr), rs779517988, ClinGen CA1144378, ClinVar RCV001813027, ExAC rs779517988, REVEL 0.94, CADD 28.70, Uncertain significance, not provided
- A115P (p.Ala115Pro), UniProt VAR 011441, Pathogenic, in CNSHA2
- R116* (p.Arg116Ter), rs971962553, TOPMed rs971962553, NCI-TCGA Cosmic COSV6136, cosmic curated COSV61360, CADD 37.00, Variant assessed as somatic; high impact.
- R116L (p.Arg116Leu), ExAC rs754441130, gnomAD rs754441130
- R116Q (p.Arg116Gln), ExAC rs754441130, gnomAD rs754441130, REVEL 0.96, CADD 31.00
- L117R (p.Leu117Arg), ExAC rs754282523, gnomAD rs754282523, REVEL 0.94, AlphaMissense 0.35
- N118S (p.Asn118Ser), TOPMed rs1489078045, REVEL 0.94, AlphaMissense 0.96, Likely pathogenic, not provided
- F119V (p.Phe119Val), Ensembl rs1553230917
- S120F (p.Ser120Phe), rs2525303590, ClinGen CA342756075, ClinVar RCV003135698, UniProt VAR 011442, REVEL 0.94, CADD 32.00, Likely pathogenic, not provided
- H121Q (p.His121Gln), Ensembl rs1572057652
- G122S (p.Gly122Ser), TOPMed rs1647545745, REVEL 0.94, CADD 28.10
- S123C (p.Ser123Cys), ExAC rs756428691, gnomAD rs756428691
- H124N (p.His124Asn), NCI-TCGA Cosmic COSV6136, REVEL 0.87, AlphaMissense 0.70, Variant assessed as somatic; moderate impact.
- H124Q (p.His124Gln), TOPMed rs1240858486, gnomAD rs1240858486, REVEL 0.72, AlphaMissense 0.63
- E125A (p.Glu125Ala), ExAC rs767598564, TOPMed rs767598564, gnomAD rs767598564, REVEL 0.68, AlphaMissense 0.95
- E125D (p.Glu125Asp), TOPMed rs1260433542
- E125Q (p.Glu125Gln), ExAC rs752905261, gnomAD rs752905261, REVEL 0.50, CADD 22.50
- Y126C (p.Tyr126Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- H127D (p.His127Asp), rs1572057427, ClinGen CA342755926, ClinVar RCV001002644, Ensembl rs1572057427, AlphaMissense 0.99, MetaLR 0.99, Uncertain significance, not specified
- H127R (p.His127Arg), rs1572057410, Ensembl rs1572057410, ClinGen CA342755920, ClinVar RCV001002382, REVEL 0.95, CADD 25.10, Uncertain significance, not specified
- E129K (p.Glu129Lys), rs773981429, ExAC rs773981429, TOPMed rs773981429, gnomAD rs773981429, REVEL 0.57, CADD 16.80, Uncertain significance, Inborn genetic diseases
- S130Y (p.Ser130Tyr), rs118204089, TOPMed rs118204089, ClinGen CA215081, ClinVar RCV000001578, AlphaMissense 0.68, MetaLR 0.97, Pathogenic, Pyruvate kinase deficiency of red cells
- A132T (p.Ala132Thr), gnomAD rs1647536192, NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, NCI-TCGA Cosmic COSV6136, REVEL 0.45, CADD 22.10, Variant assessed as somatic; moderate impact.
- N133I (p.Asn133Ile), rs770337533, ExAC rs770337533, gnomAD rs770337533, NCI-TCGA Cosmic COSV6136, REVEL 0.78, CADD 26.60, Variant assessed as somatic; moderate impact.
- N133K (p.Asn133Lys), ExAC rs749817706, TOPMed rs749817706, gnomAD rs749817706, REVEL 0.65, CADD 23.40
- V134D (p.Val134Asp), rs574051756, ExAC rs574051756, TOPMed rs574051756, gnomAD rs574051756, REVEL 0.87, CADD 27.60, Pathogenic/Likely pathogenic, PKLR-related disorder; not provided
- R135W (p.Arg135Trp), rs770175821, ClinGen CA342755819, ClinVar RCV002634313, ExAC rs770175821, REVEL 0.90, CADD 28.80, Uncertain significance, not provided
- E136* (p.Glu136Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A137T (p.Ala137Thr), gnomAD rs1452107518, REVEL 0.96, CADD 25.60
- A137V (p.Ala137Val), rs1275173660, gnomAD rs1275173660, REVEL 0.85, CADD 28.10, Uncertain significance, not provided
- V138L (p.Val138Leu), TOPMed rs1647534720, REVEL 0.37, CADD 14.80
- E139D (p.Glu139Asp), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10071, Variant assessed as somatic; moderate impact.
- E139K (p.Glu139Lys), ExAC rs748560715, TOPMed rs748560715, gnomAD rs748560715, REVEL 0.63, CADD 21.10
- E139V (p.Glu139Val), Ensembl rs757997111
- S140R (p.Ser140Arg), ExAC rs781504670, gnomAD rs781504670, REVEL 0.58, CADD 22.20
- F141L (p.Phe141Leu), Ensembl rs1553230882
- F141S (p.Phe141Ser), rs1647533800, ClinGen CA342755721, ClinVar RCV003028600, Ensembl rs1647533800, REVEL 0.83, CADD 25.90, Uncertain significance, not provided
- A142P (p.Ala142Pro), Ensembl rs1647533662
Public PKLR analysis runs
- PKLR analysis run — PKLR (1,019 variants) — completed 2026-08-21