PLPBP — 234 ClinVar variants
All ClinVar germline PLPBP variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 87 flagged for review →
13 Pathogenic · 3 Pathogenic/Likely pathogenic · 5 Likely pathogenic · 11 Conflicting · 4 Benign · 5 Benign/Likely benign · 106 Likely benign · 87 Uncertain significance
Full PLPBP gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 87
Variants where the independent computational evidence doesn't line up with the clinical picture — a QC signal for a second look, not a reclassification.
Predictors vs ClinVar 3
ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.
-
PLPBP p.Pro87Leu
Pathogenic/Likely pathogenic
Multiple submitters
epilepsy, early-onset, vitamin B6-dependent
- PLPBP p.Arg205Gln Likely pathogenic Single submitter
- PLPBP p.Arg41Gln Likely pathogenic Single submitter
Predictors agree, ClinVar conflicts 7
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
PLPBP p.Ala232Val
Conflicting
Single submitter
epilepsy, early-onset, vitamin B6-dependent
- PLPBP p.Ala262Thr Conflicting Single submitter
-
PLPBP p.Glu67Lys
Conflicting
Single submitter
epilepsy, early-onset, vitamin B6-dependent
- PLPBP p.Ile164Val Conflicting Single submitter
-
PLPBP p.Ile94Thr
Conflicting
Single submitter
epilepsy, early-onset, vitamin B6-dependent
-
PLPBP p.Pro258Leu
Conflicting
Single submitter
Inborn genetic diseases
-
PLPBP p.Ser226Pro
Conflicting
Single submitter
epilepsy, early-onset, vitamin B6-dependent
Predictors lean, ClinVar uncertain 57
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
PLPBP p.Arg205Trp
Uncertain significance
Multiple submitters
epilepsy, early-onset, vitamin B6-dependent
-
PLPBP p.Arg250Gln
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.His275Leu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Ile162Thr
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Ile183Val
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Lys121Arg
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Lys49Glu
Uncertain significance
Multiple submitters
Inborn genetic diseases
- PLPBP p.Met225Leu Uncertain significance Multiple submitters
-
PLPBP p.Phe65Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Ser253Pro
Uncertain significance
Multiple submitters
Inborn genetic diseases
- PLPBP p.Ala107Thr Uncertain significance Single submitter
- PLPBP p.Ala170Thr Uncertain significance Single submitter
-
PLPBP p.Ala227Thr
Uncertain significance
Single submitter
Inborn genetic diseases
- PLPBP p.Ala227Val Uncertain significance Single submitter
- PLPBP p.Ala272Val Uncertain significance Single submitter
-
PLPBP p.Ala57Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
PLPBP p.Arg30Gly
Uncertain significance
Single submitter
epilepsy, early-onset, vitamin B6-dependent
- PLPBP p.Arg31Trp Uncertain significance Single submitter
- PLPBP p.Asn101Asp Uncertain significance Single submitter
-
PLPBP p.Asn68Lys
Uncertain significance
Single submitter
epilepsy, early-onset, vitamin B6-dependent
- PLPBP p.Asp217Asn Uncertain significance Single submitter
- PLPBP p.Asp259Gly Uncertain significance Single submitter
- PLPBP p.Cys172Phe Uncertain significance Single submitter
- PLPBP p.Cys209Tyr Uncertain significance Single submitter
- PLPBP p.Cys86Phe Uncertain significance Single submitter
- PLPBP p.Gln273Arg Uncertain significance Single submitter
- PLPBP p.Gly187Val Uncertain significance Single submitter
-
PLPBP p.Gly243Arg
Uncertain significance
Single submitter
epilepsy, early-onset, vitamin B6-dependent
-
PLPBP p.His275Asp
Uncertain significance
Single submitter
epilepsy, early-onset, vitamin B6-dependent
- PLPBP p.His275Pro Uncertain significance Single submitter
- PLPBP p.Ile168Val Uncertain significance Single submitter
- PLPBP p.Ile242Thr Uncertain significance Single submitter
- PLPBP p.Ile38Met Uncertain significance Single submitter
-
PLPBP p.Ile38Phe
Uncertain significance
Single submitter
Inborn genetic diseases
- PLPBP p.Ile55Met Uncertain significance Single submitter
- PLPBP p.Leu212Met Uncertain significance Single submitter
-
PLPBP p.Lys266Arg
Uncertain significance
Single submitter
Inborn genetic diseases
- PLPBP p.Met106Leu Uncertain significance Single submitter
- PLPBP p.Met53Leu Uncertain significance Single submitter
- PLPBP p.Phe177Ser Uncertain significance Single submitter
-
PLPBP p.Pro109Leu
Uncertain significance
Single submitter
Inborn genetic diseases
- PLPBP p.Pro136Leu Uncertain significance Single submitter
- PLPBP p.Pro215Ala Uncertain significance Single submitter
- PLPBP p.Pro268Leu Uncertain significance Single submitter
- PLPBP p.Pro40Leu Uncertain significance Single submitter
- PLPBP p.Ser237Pro Uncertain significance Single submitter
-
PLPBP p.Ser46Asn
Uncertain significance
Single submitter
epilepsy, early-onset, vitamin B6-dependent
-
PLPBP p.Thr116Ile
Uncertain significance
Single submitter
epilepsy, early-onset, vitamin B6-dependent
- PLPBP p.Thr245Ala Uncertain significance Single submitter
- PLPBP p.Trp91Cys Uncertain significance Single submitter
- PLPBP p.Tyr58Cys Uncertain significance Single submitter
- PLPBP p.Val108Ile Uncertain significance Single submitter
- PLPBP p.Val117Ala Uncertain significance Single submitter
-
PLPBP p.Val141Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
PLPBP p.Val178Leu
Uncertain significance
Single submitter
epilepsy, early-onset, vitamin B6-dependent
-
PLPBP p.Val265Met
Uncertain significance
Single submitter
epilepsy, early-onset, vitamin B6-dependent
- PLPBP p.Val271Met Uncertain significance Single submitter
Predictors split 20
The independent predictors disagree with each other — read with care.
-
PLPBP p.Arg63Cys
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Asn110Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Cys209Gly
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Glu56Lys
Uncertain significance
Multiple submitters
Inborn genetic diseases
- PLPBP p.Gly149Arg Uncertain significance Multiple submitters
-
PLPBP p.Ile168Met
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Leu111Phe
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Leu114Met
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Thr147Ser
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Thr245Met
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
PLPBP p.Arg63His
Uncertain significance
Single submitter
Inborn genetic diseases
- PLPBP p.Glu249Lys Uncertain significance Single submitter
- PLPBP p.Met53Ile Uncertain significance Single submitter
- PLPBP p.Pro158Leu Uncertain significance Single submitter
- PLPBP p.Pro80Thr Uncertain significance Single submitter
- PLPBP p.Ser84Pro Uncertain significance Single submitter
-
PLPBP p.Val108Leu
Uncertain significance
Single submitter
Inborn genetic diseases
- PLPBP p.Val165Met Uncertain significance Single submitter
-
PLPBP p.Val235Gly
Conflicting
Single submitter
epilepsy, early-onset, vitamin B6-dependent
-
PLPBP p.Glu220Lys
Uncertain significance
No assertion criteria
PLPBP-related disorder
All PLPBP variants
Pathogenic 13
- c.320-2A>G Multiple submitters epilepsy, early-onset, vitamin B6-dependent
- p.Asp124fs Multiple submitters PLPBP & PROSC-related disorders
- p.Ser84fs Multiple submitters
- c.207+1G>A Single submitter epilepsy, early-onset, vitamin B6-dependent
- c.207+1G>C Single submitter
- p.Gln71Ter Single submitter epilepsy, early-onset, vitamin B6-dependent
- p.Gln98Ter Single submitter
- p.Met106fs Single submitter
- p.Ser78Ter Single submitter epilepsy, early-onset, vitamin B6-dependent
- p.Trp130fs Single submitter epilepsy, early-onset, vitamin B6-dependent
- p.Tyr69Ter Single submitter
- p.Val13fs Single submitter Inborn genetic diseases
- p.Leu175Pro No assertion criteria epilepsy, early-onset, vitamin B6-dependent
Pathogenic/Likely pathogenic 3
- c.207+1G>T Multiple submitters epilepsy, early-onset, vitamin B6-dependent
- p.Arg241Gln Multiple submitters epilepsy, early-onset, vitamin B6-dependent
- p.Pro87Leu Multiple submitters epilepsy, early-onset, vitamin B6-dependent ⚠
Likely pathogenic 5
- c.319+1G>C Single submitter
- p.Arg205Gln Single submitter ⚠
- p.Arg41Gln Single submitter ⚠
- p.Pro215fs Single submitter epilepsy, early-onset, vitamin B6-dependent
- p.Trp130Ter Single submitter epilepsy, early-onset, vitamin B6-dependent
Conflicting classifications of pathogenicity 11
- c.597+4C>T Single submitter
- p.Ala232Val Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Ala262Thr Single submitter ⚠
- p.Arg241Ter Single submitter epilepsy, early-onset, vitamin B6-dependent
- p.Glu67Lys Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Gly224= Single submitter
- p.Ile164Val Single submitter ⚠
- p.Ile94Thr Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Pro258Leu Single submitter Inborn genetic diseases ⚠
- p.Ser226Pro Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Val235Gly Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
Benign 4
- c.598-64T>A Multiple submitters
- c.*27A>G Multiple submitters
- c.455-10T>C Single submitter
- c.597+111T>C Single submitter
Benign/Likely benign 5
- c.243+13C>T Multiple submitters
- c.243+17_243+18del Multiple submitters
- p.Cys261= Multiple submitters
- p.His96= Multiple submitters epilepsy, early-onset, vitamin B6-dependent
- p.Met53Val Multiple submitters epilepsy, early-onset, vitamin B6-dependent
Likely benign 106
- c.100-5G>T Multiple submitters
- c.244-18T>C Multiple submitters epilepsy, early-onset, vitamin B6-dependent
- c.320-17C>T Multiple submitters
- c.455-16G>C Multiple submitters epilepsy, early-onset, vitamin B6-dependent
- p.Ala227= Multiple submitters
- p.Leu156= Multiple submitters
- p.Leu202Val Multiple submitters
- p.Lys255= Multiple submitters
- p.Ser148= Multiple submitters
- p.Thr245= Multiple submitters
- c.100-11C>T Single submitter
- c.100-13T>C Single submitter
- c.100-14T>C Single submitter
- c.100-20G>A Single submitter
- c.100-4G>T Single submitter
- c.207+10C>A Single submitter
- c.207+10C>T Single submitter
- c.207+12T>C Single submitter
- c.207+7G>A Single submitter
- c.207+8C>G Single submitter
- c.208-10G>T Single submitter
- c.208-19T>G Single submitter
- c.208-20G>C Single submitter
- c.208-7C>T Single submitter
- c.243+11A>G Single submitter
- c.243+12G>A Single submitter
- c.243+12G>C Single submitter
- c.243+14T>A Single submitter
- c.243+17A>G Single submitter
- c.243+17A>T Single submitter
- c.243+19T>C Single submitter
- c.243+20C>A Single submitter
- c.243+9A>C Single submitter
- c.243+9A>G Single submitter
- c.244-18T>A Single submitter
- c.244-19G>T Single submitter
- c.244-8C>T Single submitter
- c.319+14A>G Single submitter
- c.319+19T>A Single submitter
- c.320-12G>T Single submitter
- c.320-13dup Single submitter
- c.320-14C>G Single submitter
- c.320-19T>C Single submitter
- c.320-7A>G Single submitter
- c.454+10C>T Single submitter
- c.455-11T>C Single submitter
- c.455-13T>C Single submitter
- c.455-16G>A Single submitter
- c.455-17T>C Single submitter
- c.455-6T>G Single submitter
- c.597+11G>A Single submitter
- c.597+13C>G Single submitter
- c.597+13C>T Single submitter
- c.597+14G>A Single submitter
- c.597+17del Single submitter
- c.598-13C>T Single submitter
- c.598-5G>A Single submitter
- c.598-9_598-8del Single submitter
- c.696+13C>T Single submitter
- c.696+15A>G Single submitter
- c.696+18G>A Single submitter
- c.696+21del Single submitter
- c.697-15T>C Single submitter
- c.697-16C>A Single submitter
- c.697-18T>C Single submitter
- c.697-19C>T Single submitter
- p.Ala107= Single submitter
- p.Ala170= Single submitter
- p.Ala37= Single submitter
- p.Ala44= Single submitter
- p.Ala77= Single submitter
- p.Arg138= Single submitter
- p.Arg41= Single submitter
- p.Asn146= Single submitter
- p.Asn169= Single submitter
- p.Asp197= Single submitter
- p.Asp264= Single submitter
- p.Gln230= Single submitter
- p.Glu207= Single submitter
- p.Gly14= Single submitter
- p.Gly59= Single submitter
- p.Gly95= Single submitter
- p.His60= Single submitter
- p.His92= Single submitter
- p.Ile164= Single submitter
- p.Ile55= Single submitter
- p.Leu201= Single submitter
- p.Leu202= Single submitter
- p.Leu204= Single submitter
- p.Leu208= Single submitter
- p.Leu73= Single submitter
- p.Leu85= Single submitter
- p.Leu97= Single submitter
- p.Phe112= Single submitter
- p.Phe177= Single submitter
- p.Pro258= Single submitter
- p.Pro268= Single submitter
- p.Pro50= Single submitter
- p.Ser226= Single submitter
- p.Thr161= Single submitter
- p.Tyr69= Single submitter
- p.Val126= Single submitter
- p.Val143= Single submitter
- p.Val271= Single submitter
- p.Val43= Single submitter
- p.Val54= Single submitter
Uncertain significance 87
- p.Ala232= Multiple submitters
- p.Arg205Trp Multiple submitters epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Arg250Gln Multiple submitters Inborn genetic diseases ⚠
- p.Arg63Cys Multiple submitters Inborn genetic diseases ⚠
- p.Asn110Ser Multiple submitters Inborn genetic diseases ⚠
- p.Asp189His Multiple submitters Inborn genetic diseases
- p.Cys209Gly Multiple submitters Inborn genetic diseases ⚠
- p.Glu56Lys Multiple submitters Inborn genetic diseases ⚠
- p.Gly149Arg Multiple submitters ⚠
- p.His275Leu Multiple submitters Inborn genetic diseases ⚠
- p.Ile162Thr Multiple submitters Inborn genetic diseases ⚠
- p.Ile168Met Multiple submitters Inborn genetic diseases ⚠
- p.Ile183Val Multiple submitters Inborn genetic diseases ⚠
- p.Leu111Phe Multiple submitters Inborn genetic diseases ⚠
- p.Leu114Met Multiple submitters Inborn genetic diseases ⚠
- p.Lys121Arg Multiple submitters Inborn genetic diseases ⚠
- p.Lys49Glu Multiple submitters Inborn genetic diseases ⚠
- p.Met225Leu Multiple submitters ⚠
- p.Phe65Ser Multiple submitters Inborn genetic diseases ⚠
- p.Pro258fs Multiple submitters epilepsy, early-onset, vitamin B6-dependent
- p.Ser253Pro Multiple submitters Inborn genetic diseases ⚠
- p.Thr147Ser Multiple submitters Inborn genetic diseases ⚠
- p.Thr245Met Multiple submitters Inborn genetic diseases ⚠
- c.244-20_244-19delinsAT Single submitter
- c.454+10C>G Single submitter
- c.597+2dup Single submitter
- c.597+4C>G Single submitter
- p.Ala107Thr Single submitter ⚠
- p.Ala170Thr Single submitter ⚠
- p.Ala227Thr Single submitter Inborn genetic diseases ⚠
- p.Ala227Val Single submitter ⚠
- p.Ala272Val Single submitter ⚠
- p.Ala57Ser Single submitter Inborn genetic diseases ⚠
- p.Arg30Gly Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Arg31Trp Single submitter ⚠
- p.Arg63His Single submitter Inborn genetic diseases ⚠
- p.Asn101Asp Single submitter ⚠
- p.Asn239Asp Single submitter
- p.Asn68Lys Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Asp217Asn Single submitter ⚠
- p.Asp259Gly Single submitter ⚠
- p.Cys172Phe Single submitter ⚠
- p.Cys209Tyr Single submitter ⚠
- p.Cys86Phe Single submitter ⚠
- p.Gln273Arg Single submitter ⚠
- p.Glu249Lys Single submitter ⚠
- p.Gly187Val Single submitter ⚠
- p.Gly243Arg Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Gly248fs Single submitter
- p.His275Asp Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.His275Pro Single submitter ⚠
- p.Ile168Val Single submitter ⚠
- p.Ile242Thr Single submitter ⚠
- p.Ile38Met Single submitter ⚠
- p.Ile38Phe Single submitter Inborn genetic diseases ⚠
- p.Ile55Met Single submitter ⚠
- p.Leu212Met Single submitter ⚠
- p.Lys266Arg Single submitter Inborn genetic diseases ⚠
- p.Met106Leu Single submitter ⚠
- p.Met53Ile Single submitter ⚠
- p.Met53Leu Single submitter ⚠
- p.Phe177Ser Single submitter ⚠
- p.Pro109Leu Single submitter Inborn genetic diseases ⚠
- p.Pro136del Single submitter
- p.Pro136Leu Single submitter ⚠
- p.Pro158Leu Single submitter ⚠
- p.Pro215Ala Single submitter ⚠
- p.Pro268Leu Single submitter ⚠
- p.Pro40Leu Single submitter ⚠
- p.Pro80Thr Single submitter ⚠
- p.Ser237Pro Single submitter ⚠
- p.Ser46Asn Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Ser46Thr Single submitter Inborn genetic diseases
- p.Ser84Pro Single submitter ⚠
- p.Thr116Ile Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Thr245Ala Single submitter ⚠
- p.Trp91Cys Single submitter ⚠
- p.Tyr58Cys Single submitter ⚠
- p.Val108Ile Single submitter ⚠
- p.Val108Leu Single submitter Inborn genetic diseases ⚠
- p.Val117Ala Single submitter ⚠
- p.Val141Ile Single submitter Inborn genetic diseases ⚠
- p.Val165Met Single submitter ⚠
- p.Val178Leu Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Val265Met Single submitter epilepsy, early-onset, vitamin B6-dependent ⚠
- p.Val271Met Single submitter ⚠
- p.Glu220Lys No assertion criteria PLPBP-related disorder ⚠