HSD17B3 — 301 ClinVar variants
All ClinVar germline HSD17B3 variants across every classification, each assembled from ClinVar, gnomAD, AlphaMissense, conservation and more. 53 flagged for review →
26 Pathogenic · 10 Pathogenic/Likely pathogenic · 19 Likely pathogenic · 7 Conflicting · 32 Benign · 2 Benign/Likely benign · 150 Likely benign · 55 Uncertain significance
Full HSD17B3 gene report on Sugi Atlas → Gene function, pathways, protein structure, constraint & interactions⚑ Evidence disagreements 53
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 6
ClinVar calls these pathogenic, but the computational predictors lean tolerated — the highest-value review flag.
-
HSD17B3 p.Ala203Val
Pathogenic/Likely pathogenic
Multiple submitters
Inborn genetic diseases
-
HSD17B3 p.Gln176Pro
Pathogenic
Multiple submitters
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
-
HSD17B3 p.Glu214Gly
Pathogenic/Likely pathogenic
Multiple submitters
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
-
HSD17B3 p.Glu93Lys
Pathogenic
Multiple submitters
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
-
HSD17B3 p.Met47Val
Pathogenic/Likely pathogenic
Multiple submitters
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
-
HSD17B3 p.Thr227Ala
Pathogenic
No assertion criteria
disorder of sexual differentiation
Predictors agree, ClinVar conflicts 2
ClinVar submitters conflict, but the independent predictors unanimously agree — a QC review flag, not a reclassification.
-
HSD17B3 p.Ala200Val
Conflicting
Single submitter
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
-
HSD17B3 p.Leu68Arg
Conflicting
Single submitter
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
Predictors lean, ClinVar uncertain 37
ClinVar classifies these uncertain (VUS), but the independent predictors unanimously lean one way — a triage signal for review, not a reclassification.
-
HSD17B3 p.Asp110Tyr
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
HSD17B3 p.Lys308Thr
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
HSD17B3 p.Pro147Leu
Uncertain significance
Multiple submitters
Inborn genetic diseases
-
HSD17B3 p.Ala105Thr
Uncertain significance
Single submitter
Inborn genetic diseases
- HSD17B3 p.Ala121Thr Uncertain significance Single submitter
- HSD17B3 p.Ala275Val Uncertain significance Single submitter
- HSD17B3 p.Ala63Val Uncertain significance Single submitter
-
HSD17B3 p.Arg310Lys
Uncertain significance
Single submitter
Inborn genetic diseases
- HSD17B3 p.Asn74Ser Uncertain significance Single submitter
- HSD17B3 p.Asp110Gly Uncertain significance Single submitter
- HSD17B3 p.Cys20Phe Uncertain significance Single submitter
-
HSD17B3 p.Cys30Gly
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Glu67Lys
Uncertain significance
Single submitter
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- HSD17B3 p.Gly126Val Uncertain significance Single submitter
-
HSD17B3 p.His115Pro
Uncertain significance
Single submitter
Inborn genetic diseases
- HSD17B3 p.Ile112Val Uncertain significance Single submitter
- HSD17B3 p.Ile223Val Uncertain significance Single submitter
-
HSD17B3 p.Leu128Ser
Uncertain significance
Single submitter
pseudohermaphroditism
-
HSD17B3 p.Leu14Met
Uncertain significance
Single submitter
Inborn genetic diseases
- HSD17B3 p.Leu18Gln Uncertain significance Single submitter
-
HSD17B3 p.Leu212Arg
Uncertain significance
Single submitter
Inborn genetic diseases
- HSD17B3 p.Leu21Pro Uncertain significance Single submitter
- HSD17B3 p.Leu274Phe Uncertain significance Single submitter
-
HSD17B3 p.Lys237Glu
Uncertain significance
Single submitter
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
-
HSD17B3 p.Lys37Glu
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Lys41Gln
Uncertain significance
Single submitter
Inborn genetic diseases
- HSD17B3 p.Pro191Ser Uncertain significance Single submitter
- HSD17B3 p.Ser184Phe Uncertain significance Single submitter
-
HSD17B3 p.Ser99Arg
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Thr108Ile
Uncertain significance
Single submitter
Inborn genetic diseases
- HSD17B3 p.Thr81Pro Uncertain significance Single submitter
- HSD17B3 p.Trp50Arg Uncertain significance Single submitter
-
HSD17B3 p.Tyr299Ser
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Val161Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Val4Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Val52Ala
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Val52Glu
Uncertain significance
Single submitter
Inborn genetic diseases
Predictors split 8
The independent predictors disagree with each other — read with care.
-
HSD17B3 p.Asn130Ser
Pathogenic/Likely pathogenic
Multiple submitters
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
-
HSD17B3 p.Arg45Trp
Conflicting
Single submitter
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- HSD17B3 p.Gln224His Uncertain significance Single submitter
-
HSD17B3 p.Met134Thr
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Met164Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Thr265Ile
Uncertain significance
Single submitter
Inborn genetic diseases
-
HSD17B3 p.Thr81Met
Conflicting
Single submitter
Differences in sex development
-
HSD17B3 p.Tyr113Cys
Uncertain significance
Single submitter
46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
All HSD17B3 variants
Pathogenic 26
- c.201+1G>A Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- c.202-1G>A Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- c.277+4A>T Multiple submitters Fetal anomalies with a likely genetic cause
- c.278-1G>C Multiple submitters HSD17B3-related disorder
- p.Arg80Gln Multiple submitters Differences in sex development
- p.Gln176Pro Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Glu93Lys Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Ile244fs Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Ser232Leu Multiple submitters HSD17B3-related disorder
- c.673-1G>C Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- c.822+1G>A Single submitter
- p.Glu254fs Single submitter
- p.Glu67Ter Single submitter
- p.Gly267Ser Single submitter
- p.Ile102fs Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Ile222delinsGlnValArgTrpAlaAlaValGluSerLeuSerSerSerArgTer Single submitter
- p.Leu128Ter Single submitter
- p.Leu139fs Single submitter
- p.Lys41fs Single submitter pseudohermaphroditism
- p.Ser185_Gly186insTer Single submitter
- p.Thr54fs Single submitter
- p.Trp50Ter Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Tyr35Ter Single submitter
- c.454-1G>A No assertion criteria pseudohermaphroditism
- c.525-2del No assertion criteria 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Thr227Ala No assertion criteria disorder of sexual differentiation ⚠
Pathogenic/Likely pathogenic 10
- c.194C>T Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Ala203Val Multiple submitters Inborn genetic diseases ⚠
- p.Arg80Trp Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Asn130Ser Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Asn74Thr Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Glu118Ter Multiple submitters HSD17B3-related disorder
- p.Glu214Gly Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Met47Val Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Pro282Leu Multiple submitters Inborn genetic diseases
- p.Val225Met Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
Likely pathogenic 19
- c.154+1G>A Single submitter
- c.277+5G>A Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- c.386-2A>C Single submitter
- c.454-2A>G Single submitter
- c.672+1G>A Single submitter
- c.672+1G>T Single submitter
- p.Glu214fs Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.His271Arg Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Leu139del Single submitter pseudohermaphroditism
- p.Leu212Gln Single submitter Differences in sex development
- p.Lys37fs Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Lys84fs Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Met197Lys Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Met1Thr Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Met1Val Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Met235Val Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Trp284Ter Single submitter
- p.Met1Ile No assertion criteria disorder of sexual differentiation
- p.Pro193His No assertion criteria pseudohermaphroditism
Conflicting classifications of pathogenicity 7
- c.386-5G>A Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- c.489+9T>C Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Ala200Val Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Arg45Trp Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Asp3= Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Leu68Arg Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Thr81Met Single submitter Differences in sex development ⚠
Benign 32
- c.154+24dup Multiple submitters
- c.155-138C>T Multiple submitters
- c.201+117G>A Multiple submitters
- c.201+38T>C Multiple submitters
- c.201+86A>G Multiple submitters
- c.278-67G>A Multiple submitters
- c.453+37T>C Multiple submitters
- c.453+84G>A Multiple submitters
- c.454-284G>A Multiple submitters
- c.607-23G>C Multiple submitters
- c.607-48C>T Multiple submitters
- c.672+33A>G Multiple submitters
- c.673-75G>A Multiple submitters
- c.-10G>C Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Ser65= Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- c.154+197C>T Single submitter
- c.154+240del Single submitter
- c.154+265C>T Single submitter
- c.277+14dup Single submitter
- c.277+254T>G Single submitter
- c.278-19del Single submitter
- c.278-19dup Single submitter
- c.278-6G>A Single submitter
- c.524+280A>C Single submitter
- c.525-199C>T Single submitter
- c.607-213A>G Single submitter
- c.607-279dup Single submitter
- c.607-281G>A Single submitter
- c.822+155G>A Single submitter
- c.822+186C>T Single submitter
- c.822+285G>C Single submitter
- c.823-67_823-59del Single submitter
Benign/Likely benign 2
- p.Asp111= Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Gly289Ser Multiple submitters 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
Likely benign 150
- c.154+20C>A Multiple submitters
- c.277+13C>T Multiple submitters
- c.453+223C>T Multiple submitters
- c.524+8C>A Multiple submitters
- c.606+220C>T Multiple submitters
- p.Ser42= Multiple submitters
- c.154+14C>G Single submitter
- c.154+17T>A Single submitter
- c.154+193T>C Single submitter
- c.154+8A>G Single submitter
- c.154+9G>A Single submitter
- c.154+9G>T Single submitter
- c.155-14C>T Single submitter
- c.155-15_155-12dup Single submitter
- c.155-206dup Single submitter
- c.155-299G>A Single submitter
- c.155-308C>T Single submitter
- c.201+10C>G Single submitter
- c.201+14C>T Single submitter
- c.201+17G>T Single submitter
- c.201+19G>C Single submitter
- c.201+20A>T Single submitter
- c.201+8A>G Single submitter
- c.201+9T>C Single submitter
- c.202-11C>T Single submitter
- c.202-12T>G Single submitter
- c.202-6T>C Single submitter
- c.202-9C>T Single submitter
- c.277+14del Single submitter
- c.277+19A>G Single submitter
- c.277+9C>T Single submitter
- c.278-13G>A Single submitter
- c.278-14del Single submitter
- c.278-16G>A Single submitter
- c.278-18C>T Single submitter
- c.278-5T>G Single submitter
- c.278-7C>T Single submitter
- c.385+10T>C Single submitter
- c.385+13C>A Single submitter
- c.385+13C>T Single submitter
- c.385+17A>T Single submitter
- c.385+19G>T Single submitter
- c.385+245dup Single submitter
- c.386-13T>C Single submitter
- c.386-15G>A Single submitter
- c.386-5G>T Single submitter
- c.453+14C>T Single submitter
- c.453+161C>T Single submitter
- c.453+18T>C Single submitter
- c.453+19G>A Single submitter
- c.489+10C>G Single submitter
- c.489+11A>T Single submitter
- c.489+12A>C Single submitter
- c.489+14A>G Single submitter
- c.489+16A>G Single submitter
- c.489+7G>C Single submitter
- c.489+8A>G Single submitter
- c.490-20C>A Single submitter
- c.524+20A>C Single submitter
- c.525-11T>C Single submitter
- c.525-13C>T Single submitter
- c.525-14del Single submitter
- c.525-7C>T Single submitter
- c.525-8C>T Single submitter
- c.606+10dup Single submitter
- c.606+10G>A Single submitter
- c.606+13A>G Single submitter
- c.606+14T>C Single submitter
- c.606+17C>T Single submitter
- c.607-140A>G Single submitter
- c.607-14C>G Single submitter
- c.607-18C>G Single submitter
- c.607-270del Single submitter
- c.607-4C>T Single submitter
- c.672+19G>A Single submitter
- c.673-10C>A Single submitter
- c.673-10C>T Single submitter
- c.673-12T>C Single submitter
- c.673-20G>A Single submitter
- c.673-7G>A Single submitter
- c.673-7G>T Single submitter
- c.673-8C>T Single submitter
- c.673-9C>G Single submitter
- c.822+11A>G Single submitter
- c.822+14T>G Single submitter
- c.822+15C>G Single submitter
- c.822+39G>A Single submitter
- c.823-11C>T Single submitter
- c.823-12T>C Single submitter
- c.823-16C>T Single submitter
- p.Ala146Thr Single submitter Inborn genetic diseases
- p.Ala200= Single submitter
- p.Ala203= Single submitter
- p.Ala207= Single submitter
- p.Ala207Thr Single submitter
- p.Ala211= Single submitter
- p.Ala22= Single submitter
- p.Ala234= Single submitter
- p.Ala270= Single submitter
- p.Ala275= Single submitter
- p.Ala63= Single submitter
- p.Ala87= Single submitter
- p.Arg45= Single submitter
- p.Arg80= Single submitter
- p.Arg94= Single submitter
- p.Cys206= Single submitter
- p.Cys24= Single submitter
- p.Gln213= Single submitter
- p.Glu173= Single submitter
- p.Gly178= Single submitter
- p.Gly2= Single submitter
- p.Gly276= Single submitter
- p.Gly57= Single submitter
- p.Gly97= Single submitter
- p.Ile10= Single submitter
- p.Ile102= Single submitter
- p.Ile273= Single submitter
- p.Ile53= Single submitter
- p.Ile78= Single submitter
- p.Leu120= Single submitter
- p.Leu18= Single submitter
- p.Leu212= Single submitter
- p.Leu256= Single submitter
- p.Leu280= Single submitter
- p.Lys109= Single submitter
- p.Phe277= Single submitter
- p.Phe291= Single submitter
- p.Phe66= Single submitter
- p.Pro147= Single submitter
- p.Pro228= Single submitter
- p.Pro282= Single submitter
- p.Ser160= Single submitter
- p.Ser185= Single submitter
- p.Ser196= Single submitter
- p.Ser232= Single submitter
- p.Ser279= Single submitter
- p.Ser288= Single submitter
- p.Thr227= Single submitter
- p.Thr236= Single submitter
- p.Thr245= Single submitter
- p.Thr81= Single submitter
- p.Tyr113= Single submitter
- p.Tyr258= Single submitter
- p.Tyr64= Single submitter
- p.Val132= Single submitter
- p.Val205= Single submitter
- p.Val25= Single submitter
- p.Val38= Single submitter
- c.154+6G>A No assertion criteria HSD17B3-related disorder
- p.Arg310= No assertion criteria HSD17B3-related disorder
Uncertain significance 55
- p.Asp110Tyr Multiple submitters Inborn genetic diseases ⚠
- p.Lys308Thr Multiple submitters Inborn genetic diseases ⚠
- p.Pro147Leu Multiple submitters Inborn genetic diseases ⚠
- c.385+5G>A Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- c.490-6T>C Single submitter
- c.672+5G>A Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- c.*1C>T Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Ala105Thr Single submitter Inborn genetic diseases ⚠
- p.Ala121Thr Single submitter ⚠
- p.Ala275Val Single submitter ⚠
- p.Ala63Val Single submitter ⚠
- p.Arg310Lys Single submitter Inborn genetic diseases ⚠
- p.Asn74Ser Single submitter ⚠
- p.Asp110Gly Single submitter ⚠
- p.Cys20Phe Single submitter ⚠
- p.Cys30Gly Single submitter Inborn genetic diseases ⚠
- p.Gln224His Single submitter ⚠
- p.Glu67Lys Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Glu6fs Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Glu86_Ile88del Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Gly126Val Single submitter ⚠
- p.His115Pro Single submitter Inborn genetic diseases ⚠
- p.Ile112Val Single submitter ⚠
- p.Ile180= Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Ile223Val Single submitter ⚠
- p.Ile92= Single submitter
- p.Leu128Ser Single submitter pseudohermaphroditism ⚠
- p.Leu14Met Single submitter Inborn genetic diseases ⚠
- p.Leu18Gln Single submitter ⚠
- p.Leu212Arg Single submitter Inborn genetic diseases ⚠
- p.Leu21Pro Single submitter ⚠
- p.Leu274Phe Single submitter ⚠
- p.Lys237Glu Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Lys308Ter Single submitter
- p.Lys37Glu Single submitter Inborn genetic diseases ⚠
- p.Lys41Gln Single submitter Inborn genetic diseases ⚠
- p.Met134Thr Single submitter Inborn genetic diseases ⚠
- p.Met164Ile Single submitter Inborn genetic diseases ⚠
- p.Met164Leu Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Met1Arg Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
- p.Pro191Ser Single submitter ⚠
- p.Ser184Phe Single submitter ⚠
- p.Ser99Arg Single submitter Inborn genetic diseases ⚠
- p.Thr108Ile Single submitter Inborn genetic diseases ⚠
- p.Thr265Ile Single submitter Inborn genetic diseases ⚠
- p.Thr81Pro Single submitter ⚠
- p.Trp50Arg Single submitter ⚠
- p.Tyr113Cys Single submitter 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency ⚠
- p.Tyr299Ser Single submitter Inborn genetic diseases ⚠
- p.Val161Ile Single submitter Inborn genetic diseases ⚠
- p.Val4Ile Single submitter Inborn genetic diseases ⚠
- p.Val52Ala Single submitter Inborn genetic diseases ⚠
- p.Val52Glu Single submitter Inborn genetic diseases ⚠
- c.202-18259A>G No assertion criteria Sex development disorder
- c.385+1G>A No assertion criteria