HSD17B4 (Peroxisomal multifunctional enzyme type 2) variants and mutations
HSD17B4 (also known as Peroxisomal multifunctional enzyme type 2) is a human protein-coding gene encoding a peroxisomal multifunctional enzyme type 2 protein. A peroxisomal multifunctional enzyme that carries out two steps in fatty-acid beta-oxidation. It processes straight-chain and branched fatty acids as well as bile-acid intermediates, and loss of the protein causes D-bifunctional protein deficiency. This analysis covers 1,234 HSD17B4 variants and mutations. Of these, 97% have computational variant effect predictions. Disease context includes d-bifunctional protein deficiency, Perrault syndrome 1, and Perrault syndrome. Example HSD17B4 variants include M1I, M1L, and G2A.
Variant analysis overview
- Gene: HSD17B4
- Protein: Peroxisomal multifunctional enzyme type 2
- UniProt accession: P51659
- Organism: Homo sapiens
- Variants analyzed: 1234
- Variant scope: all variants
- Completed: 2026-05-15
Variant and mutation evidence
- Variant composition: 1,044 unspecified-consequence records; 129 missense variants; 32 synonymous variants; 9 frameshift variants; 3 in-frame deletions; 11 stop-gained variants; 1 splice-region variants; 5 substitution
- Prediction scores: 1,201 variants have prediction scores (97% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: d-bifunctional protein deficiency, Perrault syndrome 1, Perrault syndrome, genetic disorder, hearing loss, Perrault syndrome 2, DNA methylation, neurodegenerative disease, Rare genetic deafness, Abnormality of the nervous system, placenta praevia, alcohol drinking.
Protein structure and variant hotspots
- Protein features: 2 domains; 15 binding sites; 18 post-translational modification sites.
- Structural context: 344 variants have structural context.
- PTM context: 27 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, PharmGKB, MaveDB, LitVar.
Notable HSD17B4 variants
Examples include M1I, M1L, G2A, G2R, G2V, G2D, G2G, S3L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs1085307072, ClinGen CA360861571, ClinVar RCV000490425, ESM-1b 1.00, AlphaMissense 0.34, Uncertain significance, Bifunctional peroxisomal enzyme deficiency
- M1L (p.Met1Leu), rs1488399880, ClinGen CA360861558, ClinVar RCV001065701, ESM-1b 1.00, AlphaMissense 0.13, Likely pathogenic, Bifunctional peroxisomal enzyme deficiency; Perrault syndrome
- G2A (p.Gly2Ala), gnomAD rs1192300477, REVEL 0.15, ESM-1b 0.00
- G2R (p.Gly2Arg), TOPMed rs1754152891, ESM-1b 1.00, AlphaMissense 0.23
- G2V (p.Gly2Val), Ensembl rs1561419677, SIFT 0.06
- G2D (p.Gly2Asp), gnomAD 5-119452580-G-A, REVEL 0.16, ESM-1b 0.00
- G2G (p.Gly2Gly), rs1417491819, gnomAD 5-119452581-C-A, CADD 14.70
- S3L (p.Ser3Leu), cosmic curated COSV56334, gnomAD rs1754154087, REVEL 0.09, ESM-1b 0.82, Uncertain significance, Bifunctional peroxisomal enzyme deficiency
- S3S (p.Ser3Ser), gnomAD 5-119452584-A-G, CADD 15.30
- S3T (p.Ser3Thr), gnomAD 5-119452814-T-A, REVEL 0.10, MetaLR 0.16
- S3* (p.Ser3Ter), gnomAD 5-119452815-C-A, CADD 32.00
- S3N (p.Ser3Asn), rs964493746, gnomAD 5-119452818-G-A, REVEL 0.07, MetaLR 0.19
- S3C (p.Ser3Cys), gnomAD 5-119456325-A-T, REVEL 0.44, MetaLR 0.63
- P4L (p.Pro4Leu), ESP rs142889209, ExAC rs142889209, TOPMed rs142889209, gnomAD rs142889209, REVEL 0.16, ESM-1b 0.00, Likely benign
- P4R (p.Pro4Arg), rs142889209, ClinGen CA3381583, ClinVar RCV000600063, ClinVar RCV001273793, REVEL 0.11, ESM-1b 0.06, Conflicting interpretations, Inborn genetic diseases; not provided; not specified
- P4S (p.Pro4Ser), gnomAD rs1240164226, REVEL 0.16, ESM-1b 0.00
- P4P (p.Pro4Pro), rs1754154891, gnomAD 5-119452587-G-A, CADD 14.90
- P4A (p.Pro4Ala), rs1381968795, gnomAD 5-119452772-C-G, REVEL 0.12, MetaLR 0.18
- P4Q (p.Pro4Gln), gnomAD 5-119452773-C-A, REVEL 0.13, MetaLR 0.20
- P4T (p.Pro4Thr), gnomAD 5-119452796-C-A, REVEL 0.15, MetaLR 0.15
- P4H (p.Pro4His), gnomAD 5-119452806-C-A, REVEL 0.20, MetaLR 0.23
- L5R (p.Leu5Arg), TOPMed rs1158314495, gnomAD rs1158314495, REVEL 0.78, ESM-1b 1.00, Likely pathogenic, Bifunctional peroxisomal enzyme deficiency
- L5L (p.Leu5Leu), rs2126590496, gnomAD 5-119452588-C-T, CADD 20.80
- L5I (p.Leu5Ile), gnomAD 5-119452763-C-A, REVEL 0.10, MetaLR 0.21
- L5V (p.Leu5Val), gnomAD 5-119452763-C-G, REVEL 0.12, MetaLR 0.21
- L5P (p.Leu5Pro), rs767820201, gnomAD 5-119452764-T-C, REVEL 0.12, MetaLR 0.22
- R6K (p.Arg6Lys), TOPMed rs1406012759, gnomAD rs1406012759, REVEL 0.38, ESM-1b 1.00
- R6M (p.Arg6Met), TOPMed rs1406012759, gnomAD rs1406012759, REVEL 0.66, ESM-1b 1.00
- R6G (p.Arg6Gly), gnomAD 5-119452591-A-G, REVEL 0.69, ESM-1b 1.00
- R6W (p.Arg6Trp), gnomAD 5-119452591-A-T, REVEL 0.70, ESM-1b 1.00
- R6R (p.Arg6Arg), rs1480283283, gnomAD 5-119452593-G-A, CADD 14.50
- F7L (p.Phe7Leu), rs143278360, cosmic curated COSV56336, ClinGen CA360861650, ClinVar RCV003990584, ESM-1b 1.00, AlphaMissense 0.94, Uncertain significance, Perrault syndrome 1
- F7F (p.Phe7Phe), rs143278360, gnomAD 5-119452596-C-T, CADD 20.30
- D8Y (p.Asp8Tyr), gnomAD 5-119452597-G-T, REVEL 0.72, ESM-1b 1.00
- G9R (p.Gly9Arg), gnomAD rs746540197, REVEL 0.69, ESM-1b 1.00
- G9W (p.Gly9Trp), gnomAD rs746540197, REVEL 0.84, ESM-1b 1.00
- G9G (p.Gly9Gly), rs370888351, gnomAD 5-119452602-G-A, CADD 17.40
- R10R (p.Arg10Arg), rs1754157239, gnomAD 5-119452603-C-A, CADD 17.60
- R10M (p.Arg10Met), rs755416119, gnomAD 5-119452785-G-T, REVEL 0.17, MetaLR 0.21
- R10S (p.Arg10Ser), rs1204278718, gnomAD 5-119452786-G-T, REVEL 0.14, MetaLR 0.22
- R10K (p.Arg10Lys), gnomAD 5-119452788-G-A, REVEL 0.10, MetaLR 0.14
- V11A (p.Val11Ala), cosmic curated COSV56335, REVEL 0.85, ESM-1b 1.00
- V11V (p.Val11Val), rs753527768, gnomAD 5-119452608-G-T, CADD 16.10
- V11I (p.Val11Ile), rs937301893, gnomAD 5-119452757-G-A, REVEL 0.13, MetaLR 0.18
- V11F (p.Val11Phe), gnomAD 5-119452757-G-T, REVEL 0.11, MetaLR 0.21
- V12A (p.Val12Ala), gnomAD rs1338970262, REVEL 0.58, ESM-1b 0.00
- V12I (p.Val12Ile), gnomAD 5-119452609-G-A, REVEL 0.50, ESM-1b 1.00
- L13M (p.Leu13Met), rs1561419761, ClinGen CA360861710, ClinVar RCV000732016, Ensembl rs1561419761, ESM-1b 1.00, AlphaMissense 0.36, Uncertain significance, not provided
- L13Q (p.Leu13Gln), Ensembl rs1249647574, REVEL 0.91, ESM-1b 1.00
- L13V (p.Leu13Val), Ensembl rs1561419761, REVEL 0.42, ESM-1b 0.00, Uncertain significance
- L13L (p.Leu13Leu), gnomAD 5-119452612-C-T, CADD 14.90
- L13E (p.Leu13Glu), gnomAD 5-119452780-CTT-C, CADD 16.60
- L13S (p.Leu13Ser), gnomAD 5-119452782-T-C, REVEL 0.06, MetaLR 0.17
- L13F (p.Leu13Phe), rs891333978, gnomAD 5-119452783-G-T, REVEL 0.15, MetaLR 0.20
- V14A (p.Val14Ala), ExAC rs764378958, gnomAD rs764378958, ESM-1b 1.00, AlphaMissense 0.89
- V14I (p.Val14Ile), cosmic curated COSV56339, REVEL 0.37, ESM-1b 0.00
- V14G (p.Val14Gly), gnomAD 5-119452612-C-CT, CADD 17.60
- T15A (p.Thr15Ala), rs2531472105, ClinVar RCV004576745, ESM-1b 1.00, AlphaMissense 0.83, Likely pathogenic, Bifunctional peroxisomal enzyme deficiency
- T15I (p.Thr15Ile), rs1332217802, ClinGen CA360861729, ClinVar RCV002608687, Ensembl rs1332217802, ESM-1b 1.00, AlphaMissense 0.98, Uncertain significance, Bifunctional peroxisomal enzyme deficiency; Perrault syndrome
- T15T (p.Thr15Thr), rs751737033, gnomAD 5-119452620-C-T, CADD 16.70
- G16A (p.Gly16Ala), gnomAD rs1278618444, ESM-1b 1.00, AlphaMissense 0.87
- G16R (p.Gly16Arg), ESP rs137853096, ExAC rs137853096, TOPMed rs137853096, gnomAD rs137853096, REVEL 0.97, ESM-1b 1.00, Pathogenic, in DBPD
- G16S (p.Gly16Ser), rs137853096, ClinGen CA118960, ClinVar RCV000008094, ClinVar RCV000415821, REVEL 0.95, ESM-1b 1.00, Conflicting interpretations, HSD17B4-related disorder; Bifunctional peroxisomal enzyme deficiency; Perrault s
- G16G (p.Gly16Gly), rs781356187, gnomAD 5-119452623-C-G, CADD 21.20
- A17G (p.Ala17Gly), TOPMed rs1244855468, gnomAD rs1244855468, REVEL 0.70, ESM-1b 1.00
- A17P (p.Ala17Pro), ExAC rs750954413, TOPMed rs750954413, gnomAD rs750954413, REVEL 0.93, ESM-1b 1.00
- A17T (p.Ala17Thr), ExAC rs750954413, TOPMed rs750954413, gnomAD rs750954413, REVEL 0.91, ESM-1b 1.00
- A17A (p.Ala17Ala), rs756529538, gnomAD 5-119452626-G-T, CADD 3.09
- A17R (p.Ala17Arg), rs756589424, gnomAD 5-119452768-GGCAC, CADD 21.00
- A17V (p.Ala17Val), gnomAD 5-119452770-C-T, REVEL 0.25, MetaLR 0.25
- A17E (p.Ala17Glu), gnomAD 5-119452770-C-A, REVEL 0.24, MetaLR 0.27
- G18V (p.Gly18Val), rs2531472210, ClinGen CA360861745, ClinVar RCV003322722, ESM-1b 1.00, AlphaMissense 0.91, Uncertain significance, Bifunctional peroxisomal enzyme deficiency
- G18R (p.Gly18Arg), gnomAD 5-119452627-G-C, REVEL 0.87, ESM-1b 1.00
- G18G (p.Gly18Gly), rs769227162, gnomAD 5-119452629-G-A, CADD 14.90
- A19E (p.Ala19Glu), ESP rs148363262, ExAC rs148363262, TOPMed rs148363262, gnomAD rs148363262, REVEL 0.36, ESM-1b 0.47, Likely benign
- A19G (p.Ala19Gly), rs148363262, ClinGen CA501230, ClinVar RCV000215788, ClinVar RCV004020593, REVEL 0.22, ESM-1b 0.00, Likely benign, Inborn genetic diseases; not specified
- A19S (p.Ala19Ser), TOPMed rs1304273072, gnomAD rs1304273072, REVEL 0.35, ESM-1b 0.00
- A19V (p.Ala19Val), cosmic curated COSV99819, ESP rs148363262, ExAC rs148363262, TOPMed rs148363262, REVEL 0.30, ESM-1b 1.00, Likely benign
- A19T (p.Ala19Thr), gnomAD 5-119452630-G-A, REVEL 0.38, ESM-1b 1.00
- G20R (p.Gly20Arg), gnomAD rs1754165225, REVEL 0.93, ESM-1b 1.00
- G20V (p.Gly20Val), gnomAD 5-119456315-G-T, REVEL 0.88, ESM-1b 1.00
- L21R (p.Leu21Arg), gnomAD 5-119452627-G-GGG, CADD 16.50
- L21S (p.Leu21Ser), gnomAD 5-119452810-TC-T, CADD 19.60
- L21F (p.Leu21Phe), rs1180156034, gnomAD 5-119452811-C-T, REVEL 0.15, MetaLR 0.23
- L21I (p.Leu21Ile), gnomAD 5-119452811-C-A, REVEL 0.16, MetaLR 0.23
- L21L (p.Leu21Leu), gnomAD 5-119452813-C-A, CADD 1.09
- L21V (p.Leu21Val), gnomAD 5-119456317-T-G, REVEL 0.70, ESM-1b 1.00
- G22C (p.Gly22Cys), gnomAD rs794729224, REVEL 0.90, ESM-1b 1.00, no classification for the single variant
- G22S (p.Gly22Ser), cosmic curated COSV56333, REVEL 0.90, ESM-1b 1.00
- G22A (p.Gly22Ala), gnomAD 5-119456321-G-C, REVEL 0.91, ESM-1b 1.00
- R23* (p.Arg23Ter), rs765702241, ClinGen CA3381653, NCI-TCGA Cosmic COSV5633, cosmic curated COSV56338, REVEL 0.27, MetaLR 0.09, Pathogenic
- R23G (p.Arg23Gly), rs765702241, ClinGen CA3381652, ClinVar RCV003058842, ClinVar RCV004070266, REVEL 0.12, ESM-1b 1.00, Uncertain significance, Perrault syndrome; Bifunctional peroxisomal enzyme deficiency; Inborn genetic di
- R23L (p.Arg23Leu), ExAC rs762613990, TOPMed rs762613990, gnomAD rs762613990, REVEL 0.69, ESM-1b 1.00, Uncertain significance
- R23Q (p.Arg23Gln), ExAC rs762613990, TOPMed rs762613990, gnomAD rs762613990, REVEL 0.51, ESM-1b 1.00, Uncertain significance, Perrault syndrome; Bifunctional peroxisomal enzyme deficiency; Perrault syndrome
- A24D (p.Ala24Asp), gnomAD 5-119456327-C-A, REVEL 0.70, ESM-1b 0.63
- A24V (p.Ala24Val), gnomAD 5-119456327-C-T, REVEL 0.81, ESM-1b 0.00
- A24A (p.Ala24Ala), rs2126610379, gnomAD 5-119456328-C-T, CADD 9.43
- Y25C (p.Tyr25Cys), Ensembl rs2126610386, REVEL 0.63, ESM-1b 1.00, Uncertain significance, Perrault syndrome 1
- A26P (p.Ala26Pro), ExAC rs751186437, TOPMed rs751186437, gnomAD rs751186437, REVEL 0.88, ESM-1b 1.00, Uncertain significance
- A26S (p.Ala26Ser), rs751186437, ClinGen CA360859923, ClinVar RCV003365967, ExAC rs751186437, REVEL 0.80, ESM-1b 0.94, Uncertain significance, Inborn genetic diseases
- A26V (p.Ala26Val), Ensembl rs1754652049, REVEL 0.78, ESM-1b 1.00
- A26T (p.Ala26Thr), gnomAD 5-119456332-G-A, REVEL 0.85, ESM-1b 1.00
- A28G (p.Ala28Gly), TOPMed rs1034994864, REVEL 0.52, ESM-1b 1.00
- A28T (p.Ala28Thr), cosmic curated COSV10608, REVEL 0.40, ESM-1b 1.00
- A28D (p.Ala28Asp), gnomAD 5-119456339-C-A, REVEL 0.56, ESM-1b 1.00
- A28V (p.Ala28Val), gnomAD 5-119456339-C-T, REVEL 0.39, ESM-1b 1.00
- F29L (p.Phe29Leu), ExAC rs780598694, gnomAD rs780598694, REVEL 0.34, ESM-1b 1.00
- F29S (p.Phe29Ser), ESP rs373805649, ExAC rs373805649, TOPMed rs373805649, gnomAD rs373805649, REVEL 0.79, ESM-1b 1.00, Uncertain significance, Bifunctional peroxisomal enzyme deficiency
- A30S (p.Ala30Ser), gnomAD 5-119456344-G-T, REVEL 0.65, ESM-1b 1.00
- A30V (p.Ala30Val), gnomAD 5-119456345-C-T, REVEL 0.77, ESM-1b 1.00
- E31* (p.Glu31Ter), cosmic curated COSV56339
- E31K (p.Glu31Lys), TOPMed rs1188838605, gnomAD rs1188838605, REVEL 0.40, ESM-1b 1.00, Uncertain significance, Perrault syndrome; Bifunctional peroxisomal enzyme deficiency
- E31G (p.Glu31Gly), gnomAD 5-119452767-A-G, REVEL 0.15, MetaLR 0.19
- E31E (p.Glu31Glu), rs1561420145, gnomAD 5-119452768-G-A, CADD 4.46
- E31D (p.Glu31Asp), gnomAD 5-119452768-G-C, REVEL 0.12, MetaLR 0.20
- E31Q (p.Glu31Gln), gnomAD 5-119452793-G-C, REVEL 0.08, MetaLR 0.17
- R32G (p.Arg32Gly), 1000Genomes rs192005316, REVEL 0.79, ESM-1b 1.00
- G33E (p.Gly33Glu), ExAC rs780129984, gnomAD rs780129984, REVEL 0.90, ESM-1b 1.00
- G33R (p.Gly33Arg), ExAC rs749921409, gnomAD rs749921409, REVEL 0.89, ESM-1b 1.00
- G33C (p.Gly33Cys), rs1754652365, gnomAD 5-119456337-G-T, REVEL 0.37, MetaLR 0.38
- A34V (p.Ala34Val), ExAC rs587777442, TOPMed rs587777442, gnomAD rs587777442, REVEL 0.76, ESM-1b 1.00, Pathogenic/Likely pathogenic, Bifunctional peroxisomal enzyme deficiency; Perrault syndrome; not provided
- A34E (p.Ala34Glu), gnomAD 5-119456357-C-A, REVEL 0.86, ESM-1b 1.00
- L35V (p.Leu35Val), TOPMed rs1235253926, gnomAD rs1235253926, REVEL 0.29, ESM-1b 0.00
- V36F (p.Val36Phe), cosmic curated COSV56338, REVEL 0.80, ESM-1b 1.00
- V36I (p.Val36Ile), TOPMed rs1210011520, gnomAD rs1210011520, REVEL 0.60, ESM-1b 1.00
- V37F (p.Val37Phe), rs747214551, ClinGen CA360860010, ClinVar RCV004404481, ClinVar RCV004775553, REVEL 0.73, ESM-1b 1.00, Uncertain significance, not provided; Inborn genetic diseases
- V37I (p.Val37Ile), rs747214551, ClinGen CA3381664, ClinVar RCV000614923, ClinVar RCV000734981, REVEL 0.26, ESM-1b 1.00, Conflicting interpretations, Inborn genetic diseases; Bifunctional peroxisomal enzyme deficiency; Perrault sy
- V37V (p.Val37Val), rs771141287, gnomAD 5-119456367-T-C, MetaLR 0.61, MetaSVM 0.30
- V38A (p.Val38Ala), Ensembl rs1748302295, REVEL 0.38, ESM-1b 1.00
- V38I (p.Val38Ile), rs778708979, gnomAD 5-119456358-G-A, REVEL 0.34, ESM-1b 1.00
- V38del (p.Val38del), gnomAD 5-119456361-AGTT-, CADD 19.50
- V38L (p.Val38Leu), gnomAD 5-119456368-G-C, REVEL 0.59, ESM-1b 1.00
- N39H (p.Asn39His), gnomAD rs1748302526, REVEL 0.77, ESM-1b 1.00
- N39S (p.Asn39Ser), gnomAD rs1274306053, REVEL 0.75, ESM-1b 1.00
- N39Y (p.Asn39Tyr), gnomAD 5-119471643-A-T, REVEL 0.25, MetaLR 0.21
- N39K (p.Asn39Lys), gnomAD 5-119471645-T-A, REVEL 0.12, MetaLR 0.18
- N39D (p.Asn39Asp), gnomAD 5-119471652-A-G, REVEL 0.17, MetaLR 0.19
- N39T (p.Asn39Thr), gnomAD 5-119471654-TA-T, CADD 14.10
- D40N (p.Asp40Asn), Ensembl rs34959311, REVEL 0.82, ESM-1b 1.00, Uncertain significance
- D40Y (p.Asp40Tyr), rs34959311, ClinGen CA360864311, ClinVar RCV002027809, Ensembl rs34959311, REVEL 0.94, ESM-1b 1.00, Uncertain significance, Bifunctional peroxisomal enzyme deficiency; Perrault syndrome
- L41I (p.Leu41Ile), gnomAD 5-119471646-C-A, REVEL 0.13, MetaLR 0.21
- L41L (p.Leu41Leu), rs1756380129, gnomAD 5-119471646-C-T, CADD 0.17
- L41V (p.Leu41Val), gnomAD 5-119471646-C-G, REVEL 0.09, MetaLR 0.21
- L41P (p.Leu41Pro), gnomAD 5-119471647-T-C, REVEL 0.22, MetaLR 0.23
- G42R (p.Gly42Arg), Ensembl rs1748303750, REVEL 0.89, ESM-1b 1.00
- G43E (p.Gly43Glu), TOPMed rs1748304186, REVEL 0.58, ESM-1b 1.00, Uncertain significance, Bifunctional peroxisomal enzyme deficiency; Perrault syndrome
- D44V (p.Asp44Val), rs200063597, ClinGen CA125857517, ClinVar RCV001882203, Ensembl rs200063597, REVEL 0.70, ESM-1b 1.00, Uncertain significance, Perrault syndrome; Bifunctional peroxisomal enzyme deficiency
- F45Y (p.Phe45Tyr), cosmic curated COSV56335, REVEL 0.17, ESM-1b 0.00
- F45L (p.Phe45Leu), gnomAD 5-119471637-T-C, REVEL 0.21, MetaLR 0.20
- F45V (p.Phe45Val), gnomAD 5-119471637-T-G, REVEL 0.16, MetaLR 0.19
- F45S (p.Phe45Ser), rs1373435837, gnomAD 5-119471638-T-C, REVEL 0.13, MetaLR 0.19
- F45D (p.Phe45Asp), rs1756386792, gnomAD 5-119471690-CTTT-, CADD 6.06
- F45C (p.Phe45Cys), gnomAD 5-119471690-CTT-C, CADD 19.70
- F45I (p.Phe45Ile), gnomAD 5-119471691-T-A, REVEL 0.17, MetaLR 0.19
- K46R (p.Lys46Arg), Ensembl rs936572362, REVEL 0.20, ESM-1b 0.76
- K46Q (p.Lys46Gln), gnomAD 5-119452790-A-C, REVEL 0.11, MetaLR 0.23
- K46T (p.Lys46Thr), gnomAD 5-119452791-A-C, REVEL 0.11, MetaLR 0.21
- K46K (p.Lys46Lys), rs1243356358, gnomAD 5-119452792-A-G, CADD 6.07
- G49V (p.Gly49Val), TOPMed rs1748308164, REVEL 0.86, ESM-1b 1.00
- K50E (p.Lys50Glu), gnomAD 5-119471667-A-G, REVEL 0.18, MetaLR 0.25
- K50* (p.Lys50Ter), rs532183192, gnomAD 5-119471667-A-T, CADD 35.00, SIFT 0.65
- K50R (p.Lys50Arg), gnomAD 5-119471668-A-G, REVEL 0.15, MetaLR 0.17
- G51A (p.Gly51Ala), 1000Genomes rs566990969, ExAC rs566990969, TOPMed rs566990969, gnomAD rs566990969, REVEL 0.33, ESM-1b 0.00
- G51V (p.Gly51Val), 1000Genomes rs566990969, ExAC rs566990969, TOPMed rs566990969, gnomAD rs566990969, REVEL 0.38, ESM-1b 1.00
- S52F (p.Ser52Phe), NCI-TCGA Cosmic COSV9982, cosmic curated COSV99820, REVEL 0.63, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- S52G (p.Ser52Gly), rs749165759, gnomAD 5-119456355-A-G, REVEL 0.37, MetaLR 0.26
- S52P (p.Ser52Pro), gnomAD 5-119471676-T-C, REVEL 0.22, MetaLR 0.27
- S52L (p.Ser52Leu), gnomAD 5-119471677-C-T, REVEL 0.24, MetaLR 0.19
- S52* (p.Ser52Ter), gnomAD 5-119471677-C-A, CADD 25.50, SIFT 0.52
- A54D (p.Ala54Asp), rs141517981, ClinGen CA3381703, ClinVar RCV000283002, ClinVar RCV000342721, REVEL 0.82, ESM-1b 1.00, Uncertain significance, Inborn genetic diseases; Bifunctional peroxisomal enzyme deficiency; Perrault sy
- A54G (p.Ala54Gly), rs141517981, ClinGen CA3381704, ClinVar RCV001926196, ESP rs141517981, REVEL 0.62, ESM-1b 1.00, Uncertain significance, Bifunctional peroxisomal enzyme deficiency; Perrault syndrome
- A54T (p.Ala54Thr), rs758207228, ClinGen CA3381701, ClinVar RCV001942349, ClinVar RCV004587228, REVEL 0.68, ESM-1b 1.00, Uncertain significance, HSD17B4-related disorder; Bifunctional peroxisomal enzyme deficiency; Perrault s
- A54V (p.Ala54Val), rs141517981, ClinGen CA3381702, ClinVar RCV002301020, ClinVar RCV003097882, REVEL 0.58, ESM-1b 1.00, Uncertain significance, not provided; Perrault syndrome; Bifunctional peroxisomal enzyme deficiency
- A55T (p.Ala55Thr), rs780149071, ClinGen CA3381705, ClinVar RCV002012223, ExAC rs780149071, REVEL 0.80, ESM-1b 1.00, Uncertain significance, Perrault syndrome; Bifunctional peroxisomal enzyme deficiency
- K57M (p.Lys57Met), cosmic curated COSV56338, REVEL 0.68, ESM-1b 0.00
- V58A (p.Val58Ala), cosmic curated COSV56338, ESM-1b 1.00, AlphaMissense 0.42, Uncertain significance, Perrault syndrome; Bifunctional peroxisomal enzyme deficiency
- V58F (p.Val58Phe), rs2126682652, ClinGen CA360864427, ClinVar RCV001356957, Ensembl rs2126682652, ESM-1b 1.00, AlphaMissense 0.89, not provided, Perrault syndrome
- V59I (p.Val59Ile), rs375339818, ClinGen CA243164, ClinVar RCV000177063, ClinVar RCV002516725, REVEL 0.61, ESM-1b 1.00, Uncertain significance, not provided; Bifunctional peroxisomal enzyme deficiency; Perrault syndrome
- V59L (p.Val59Leu), gnomAD 5-119471694-G-C, REVEL 0.33, MetaLR 0.54
- V59A (p.Val59Ala), gnomAD 5-119471695-T-C, REVEL 0.25, MetaLR 0.78
Public HSD17B4 analysis runs
- HSD17B4 analysis run — HSD17B4 (1,234 variants) — completed 2026-05-15