HMBS (Porphobilinogen deaminase) variants and mutations
HMBS (also known as Porphobilinogen deaminase) is a human protein-coding gene encoding a porphobilinogen deaminase protein. An enzyme in heme biosynthesis that joins four porphobilinogen molecules to form hydroxymethylbilane. This step is required to build the tetrapyrrole framework of heme, and HMBS dysfunction causes acute intermittent porphyria. This analysis covers 556 HMBS variants and mutations. Of these, 97% have computational variant effect predictions. Disease context includes acute intermittent porphyria, encephalopathy, porphyria-related, and leukoencephalopathy, porphyria-related. Example HMBS variants include M1V, S2P, and S2A.
Variant analysis overview
- Gene: HMBS
- Protein: Porphobilinogen deaminase
- UniProt accession: P08397
- Organism: Homo sapiens
- Variants analyzed: 556
- Variant scope: all variants
- Completed: 2026-05-30
Variant and mutation evidence
- Variant composition: 491 unspecified-consequence records; 26 missense variants; 28 synonymous variants; 2 splice-region variants; 5 frameshift variants; 4 substitution
- Prediction scores: 540 variants have prediction scores (97% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: acute intermittent porphyria, encephalopathy, porphyria-related, leukoencephalopathy, porphyria-related, neurodegenerative disease, Leukoencephalopathy, coronary artery disease, Abdominal pain, cerebellar ataxia, hereditary peripheral neuropathy, type 2 diabetes mellitus, smoking initiation, heart failure.
Protein structure and variant hotspots
- Protein features: 6 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, ClinGen, PharmGKB, MaveDB, LitVar.
Notable HMBS variants
Examples include M1V, S2P, S2A, S2F, S2Y, S2S, G3S, G3V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1V (p.Met1Val), rs118204118, ClinGen CA115020, ClinVar RCV000001549, ClinVar RCV001851553, ESM-1b 0.00, AlphaMissense 0.09, Conflicting interpretations, not provided; Acute intermittent porphyria
- S2P (p.Ser2Pro), rs1361338844, ClinGen CA382985689, ClinVar RCV002599395, gnomAD rs1361338844, REVEL 0.57, ESM-1b 0.00, Uncertain significance, not provided
- S2A (p.Ser2Ala), gnomAD 11-119085037-T-G, REVEL 0.35, ESM-1b 0.00
- S2F (p.Ser2Phe), gnomAD 11-119085038-C-T, REVEL 0.53, ESM-1b 0.71
- S2Y (p.Ser2Tyr), gnomAD 11-119085038-C-A, REVEL 0.52, ESM-1b 0.90
- S2S (p.Ser2Ser), gnomAD 11-119085039-T-C, CADD 14.20
- G3S (p.Gly3Ser), ExAC rs782528817, gnomAD rs782528817, REVEL 0.32, ESM-1b 0.00
- G3V (p.Gly3Val), ExAC rs782577135, gnomAD rs782577135, REVEL 0.33, ESM-1b 0.00
- G5S (p.Gly5Ser), rs1565750711, ClinGen CA382985736, ClinVar RCV001198784, Ensembl rs1565750711, REVEL 0.39, ESM-1b 0.00, Uncertain significance, Acute intermittent porphyria
- G5C (p.Gly5Cys), gnomAD 11-119085046-G-T, REVEL 0.46, ESM-1b 0.19
- G5D (p.Gly5Asp), gnomAD 11-119085047-G-A, REVEL 0.41, ESM-1b 0.00
- G5G (p.Gly5Gly), gnomAD 11-119085048-C-G, CADD 14.10
- N6H (p.Asn6His), gnomAD rs1397152294, REVEL 0.36, ESM-1b 0.00
- N6S (p.Asn6Ser), gnomAD 11-119085050-A-G, REVEL 0.30, ESM-1b 0.00
- N6N (p.Asn6Asn), gnomAD 11-119085051-T-C, CADD 9.57
- A7E (p.Ala7Glu), TOPMed rs1315378927, gnomAD rs1315378927, REVEL 0.42, ESM-1b 0.00
- A7V (p.Ala7Val), gnomAD 11-119085053-C-T, REVEL 0.40, ESM-1b 0.00
- A8D (p.Ala8Asp), gnomAD rs1341756409, REVEL 0.34, ESM-1b 0.00
- A8T (p.Ala8Thr), rs2497397122, ClinGen CA382985779, ClinVar RCV002986633, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, Inborn genetic diseases
- A8V (p.Ala8Val), gnomAD 11-119085056-C-T, REVEL 0.39, ESM-1b 0.00
- A9E (p.Ala9Glu), rs148084355, ClinGen CA6313828, cosmic curated COSV53828, ClinVar RCV000605528, REVEL 0.46, ESM-1b 0.00, Conflicting interpretations, not provided; not specified; Acute intermittent porphyria
- A9T (p.Ala9Thr), rs2497397150, ClinGen CA382985795, ClinVar RCV003057512, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, not provided
- A9P (p.Ala9Pro), gnomAD 11-119085058-G-C, REVEL 0.40, ESM-1b 0.00
- A9A (p.Ala9Ala), rs782487780, gnomAD 11-119085060-A-G, CADD 10.70
- T10K (p.Thr10Lys), ExAC rs782647894, TOPMed rs782647894, gnomAD rs782647894, REVEL 0.38, ESM-1b 0.00, Uncertain significance
- T10M (p.Thr10Met), rs782647894, ClinGen CA6313831, ClinVar RCV002967423, ExAC rs782647894, REVEL 0.35, ESM-1b 0.00, Conflicting interpretations, not provided
- T10P (p.Thr10Pro), TOPMed rs914471864, REVEL 0.42, ESM-1b 0.00
- T10T (p.Thr10Thr), rs782243560, gnomAD 11-119085063-G-C, CADD 7.42
- A11T (p.Ala11Thr), rs142812375, ClinGen CA6313833, ClinVar RCV002180348, 1000Genomes rs142812375, REVEL 0.35, ESM-1b 0.00, Likely benign, not provided
- A11V (p.Ala11Val), rs2497397284, ClinGen CA382985835, ClinVar RCV003690529, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, not provided
- A11A (p.Ala11Ala), gnomAD 11-119085066-G-T, CADD 31.00
- E12A (p.Glu12Ala), rs759804278, ClinGen CA6313885, ClinVar RCV002766335, ClinVar RCV004700825, REVEL 0.44, ESM-1b 0.00, Uncertain significance, not provided; not specified
- E13* (p.Glu13Ter), NCI-TCGA Cosmic COSV9959, cosmic curated COSV99598, Variant assessed as somatic; high impact.
- E13G (p.Glu13Gly), rs2497421539, ClinGen CA382888019, ClinVar RCV003388509, ESM-1b 0.00, AlphaMissense 0.05, Uncertain significance, not specified
- E13K (p.Glu13Lys), TOPMed rs1946134354, REVEL 0.40, ESM-1b 0.00
- N14T (p.Asn14Thr), rs1592212904, gnomAD 11-119088258-GA-G, CADD 24.80
- N14N (p.Asn14Asn), rs369183430, gnomAD 11-119088263-C-T, CADD 14.10
- S15S (p.Ser15Ser), gnomAD 11-119088266-C-T, CADD 13.30
- P16R (p.Pro16Arg), gnomAD rs1294868119, REVEL 0.32, ESM-1b 0.00
- K17T (p.Lys17Thr), gnomAD 11-119088271-A-C, REVEL 0.39, ESM-1b 0.00
- M18I (p.Met18Ile), cosmic curated COSV10639, NCI-TCGA TCGA novel, UniProt VAR 025558, REVEL 0.57, ESM-1b 0.00, Pathogenic, in AIP
- R19G (p.Arg19Gly), TOPMed rs776517940, REVEL 0.72, ESM-1b 1.00
- R19T (p.Arg19Thr), rs2497421693, ClinGen CA382888096, ClinVar RCV003039815, REVEL 0.43, ESM-1b 0.48, Uncertain significance, not provided
- R19S (p.Arg19Ser), rs1034391830, gnomAD 11-119088274-TGA-, CADD 28.50
- R19R (p.Arg19Arg), rs1359618302, gnomAD 11-119088278-A-G, CADD 16.30
- V20L (p.Val20Leu), gnomAD rs1399090942, REVEL 0.60, ESM-1b 0.00
- V20M (p.Val20Met), gnomAD 11-119088279-G-A, REVEL 0.76, ESM-1b 0.28
- V20E (p.Val20Glu), gnomAD 11-119088280-T-A, REVEL 0.77, ESM-1b 1.00
- V20V (p.Val20Val), rs1278601312, gnomAD 11-119088281-G-A, CADD 13.80
- I21F (p.Ile21Phe), rs1946135275, ClinGen CA382888108, ClinVar RCV001218766, Ensembl rs1946135275, REVEL 0.86, ESM-1b 0.10, Uncertain significance, not provided
- I21I (p.Ile21Ile), rs771816709, gnomAD 11-119088284-T-C, CADD 14.20
- R22C (p.Arg22Cys), rs189159450, ClinGen CA6313887, cosmic curated COSV53828, ClinVar RCV001809135, REVEL 0.95, ESM-1b 1.00, Conflicting interpretations, Acute intermittent porphyria; not provided
- R22G (p.Arg22Gly), 1000Genomes rs189159450, ExAC rs189159450, TOPMed rs189159450, gnomAD rs189159450, REVEL 0.83, ESM-1b 1.00, Pathogenic, in AIP
- R22H (p.Arg22His), rs760087108, ClinGen CA6313888, ClinVar RCV001959394, ClinVar RCV003401983, REVEL 0.86, ESM-1b 1.00, Uncertain significance, not specified; Acute intermittent porphyria; not provided
- R22R (p.Arg22Arg), rs531691068, gnomAD 11-119088287-C-T, CADD 3.83
- V23A (p.Val23Ala), TOPMed rs1432928162, gnomAD rs1432928162, REVEL 0.91, ESM-1b 0.42
- V23M (p.Val23Met), rs776931683, ClinGen CA6313890, NCI-TCGA Cosmic COSV9959, cosmic curated COSV99597, REVEL 0.69, ESM-1b 1.00, Uncertain significance, not provided; not specified
- V23L (p.Val23Leu), gnomAD 11-119088288-G-C, REVEL 0.71, ESM-1b 1.00
- V23V (p.Val23Val), rs1240518079, gnomAD 11-119088290-G-T, CADD 10.80
- G24D (p.Gly24Asp), rs2497421927, ClinGen CA382888137, ClinVar RCV003062461, ESM-1b 1.00, AlphaMissense 1.00, Likely pathogenic, not provided
- G24S (p.Gly24Ser), UniProt VAR 011001, ESM-1b 1.00, AlphaMissense 0.97, Pathogenic, in AIP
- G24V (p.Gly24Val), rs2497421927, ClinGen CA382888139, ClinVar RCV003575388, ESM-1b 1.00, AlphaMissense 0.99, Uncertain significance, not provided
- G24A (p.Gly24Ala), gnomAD 11-119088292-G-C, REVEL 0.88, ESM-1b 1.00
- G24G (p.Gly24Gly), rs1229936086, gnomAD 11-119088293-T-G, CADD 8.35
- T25I (p.Thr25Ile), rs2497421979, ClinGen CA382888148, ClinVar RCV003873131, ESM-1b 1.00, AlphaMissense 1.00, Uncertain significance, not provided
- T25T (p.Thr25Thr), rs1252084629, gnomAD 11-119088296-C-T, CADD 14.10
- R26C (p.Arg26Cys), rs998842815, ClinGen CA229592849, ClinVar RCV000799514, ClinVar RCV003152734, REVEL 0.91, ESM-1b 1.00, Pathogenic/Likely pathogenic, not provided; Acute intermittent porphyria
- R26H (p.Arg26His), rs118204103, ClinGen CA251791, cosmic curated COSV53828, ClinVar RCV000001508, REVEL 0.97, ESM-1b 1.00, Pathogenic, not provided
- R26L (p.Arg26Leu), rs118204103, ClinGen CA382888156, ClinVar RCV000824246, TOPMed rs118204103, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic, not provided
- R26P (p.Arg26Pro), rs118204103, ClinGen CA382888155, ClinVar RCV001216002, TOPMed rs118204103, ESM-1b 1.00, AlphaMissense 0.99, Likely pathogenic, not provided
- R26R (p.Arg26Arg), gnomAD 11-119088299-C-G, CADD 8.34
- K27N (p.Lys27Asn), gnomAD 11-119088301-A-AT, CADD 32.00
- S28G (p.Ser28Gly), NCI-TCGA TCGA novel, ESM-1b 1.00, AlphaMissense 0.94, Variant assessed as somatic; moderate impact., in AIP
- S28N (p.Ser28Asn), UniProt VAR 011003, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic, in AIP
- S28R (p.Ser28Arg), NCI-TCGA Cosmic COSV9959, cosmic curated COSV99598, REVEL 0.96, ESM-1b 1.00, Variant assessed as somatic; moderate impact., in AIP
- S28S (p.Ser28Ser), rs762409662, gnomAD 11-119088305-C-T, CADD 13.90
- Q29R (p.Gln29Arg), rs2497422220, ClinGen CA382888196, ClinVar RCV003677572, ESM-1b 1.00, AlphaMissense 0.29, Uncertain significance, not provided
- L30F (p.Leu30Phe), UniProt VAR 087876, REVEL 0.94, ESM-1b 1.00, Pathogenic, in AIP
- L30I (p.Leu30Ile), gnomAD 11-119088635-C-A, REVEL 0.88, ESM-1b 1.00
- A31P (p.Ala31Pro), UniProt VAR 011004, REVEL 0.99, ESM-1b 1.00, Pathogenic, in AIP
- A31T (p.Ala31Thr), rs118204104, ClinGen CA251809, ClinVar RCV000001519, UniProt VAR 003640, REVEL 0.98, ESM-1b 1.00, Pathogenic, Acute intermittent porphyria
- A31D (p.Ala31Asp), gnomAD 11-119088639-C-A, REVEL 0.98, ESM-1b 1.00
- A31A (p.Ala31Ala), gnomAD 11-119088640-T-C, CADD 9.41
- R32C (p.Arg32Cys), rs779792232, ClinGen CA6313905, NCI-TCGA Cosmic COSV5383, cosmic curated COSV53830, REVEL 0.85, ESM-1b 0.00, Uncertain significance, not provided
- R32H (p.Arg32His), rs746673847, ClinGen CA6313906, NCI-TCGA Cosmic COSV5383, cosmic curated COSV53830, REVEL 0.89, ESM-1b 1.00, Uncertain significance, not provided
- R32L (p.Arg32Leu), rs746673847, ClinGen CA382888271, ClinVar RCV003574590, ESM-1b 0.00, AlphaMissense 0.19, Uncertain significance, not provided
- R32P (p.Arg32Pro), UniProt VAR 074151, REVEL 0.92, ESM-1b 1.00, Pathogenic, in AIP
- R32Y (p.Arg32Tyr), gnomAD 11-119088637-TGCT, CADD 31.00
- R32R (p.Arg32Arg), gnomAD 11-119088643-C-A, CADD 11.20
- I33M (p.Ile33Met), 1000Genomes rs556420446, ExAC rs556420446, gnomAD rs556420446, REVEL 0.84, ESM-1b 1.00
- I33T (p.Ile33Thr), NCI-TCGA TCGA novel, REVEL 0.80, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- I33V (p.Ile33Val), gnomAD 11-119088644-A-G, REVEL 0.65, ESM-1b 0.00
- Q34K (p.Gln34Lys), rs118204105, ClinGen CA251811, ClinVar RCV000001520, UniProt VAR 003641, ESM-1b 1.00, AlphaMissense 0.96, Pathogenic, Acute intermittent porphyria
- Q34P (p.Gln34Pro), UniProt VAR 011005, ESM-1b 1.00, AlphaMissense 0.96, Pathogenic, in AIP
- Q34R (p.Gln34Arg), UniProt VAR 025559, REVEL 0.99, ESM-1b 1.00, Pathogenic, in AIP
- T35A (p.Thr35Ala), TOPMed rs1946151088, REVEL 0.91, ESM-1b 1.00
- T35M (p.Thr35Met), rs974712040, ClinGen CA229593101, NCI-TCGA Cosmic COSV5382, cosmic curated COSV53828, REVEL 0.98, ESM-1b 1.00, Likely pathogenic, not provided; Acute intermittent porphyria
- T35T (p.Thr35Thr), rs370081222, gnomAD 11-119088652-G-C, CADD 8.85
- D36D (p.Asp36Asp), gnomAD 11-119088655-C-T, CADD 14.00
- S37N (p.Ser37Asn), rs2497426121, ClinGen CA382888374, ClinVar RCV003547020, NCI-TCGA TCGA novel, ESM-1b 0.35, AlphaMissense 0.17, Uncertain significance, not provided
- S37G (p.Ser37Gly), gnomAD 11-119088656-A-G, REVEL 0.70, ESM-1b 1.00
- S37S (p.Ser37Ser), rs1946151237, gnomAD 11-119088658-T-C, CADD 12.30
- V39M (p.Val39Met), gnomAD 11-119088662-G-A, REVEL 0.75, ESM-1b 0.09
- V39A (p.Val39Ala), gnomAD 11-119088663-T-C, REVEL 0.54, ESM-1b 1.00
- A40T (p.Ala40Thr), gnomAD rs1362244070, REVEL 0.46, ESM-1b 0.25, Uncertain significance, not provided
- A40V (p.Ala40Val), ESP rs146023979, TOPMed rs146023979, gnomAD rs146023979, REVEL 0.48, ESM-1b 1.00
- T41P (p.Thr41Pro), gnomAD rs1333436762, REVEL 0.53, ESM-1b 1.00
- L42F (p.Leu42Phe), ExAC rs773769579, gnomAD rs773769579, REVEL 0.94, ESM-1b 1.00
- L42M (p.Leu42Met), rs373652991, ClinGen CA382888453, ClinVar RCV002596985, ESP rs373652991, REVEL 0.84, ESM-1b 1.00, Uncertain significance, not provided
- L42S (p.Leu42Ser), rs2497426310, ClinGen CA382888459, ClinVar RCV003062462, UniProt VAR 011007, REVEL 0.99, ESM-1b 1.00, Pathogenic, not provided
- L42I (p.Leu42Ile), rs1359742005, gnomAD 11-119088669-C-CA, CADD 23.70
- L42L (p.Leu42Leu), rs373652991, gnomAD 11-119088671-T-C, CADD 10.30
- L42W (p.Leu42Trp), gnomAD 11-119088672-T-G, REVEL 0.98, ESM-1b 1.00
- A44V (p.Ala44Val), gnomAD rs1241174663, REVEL 0.49, ESM-1b 1.00
- A44A (p.Ala44Ala), rs563428135, gnomAD 11-119088679-C-T, CADD 8.20
- S45L (p.Ser45Leu), rs138776835, ClinGen CA6313913, cosmic curated COSV53828, ClinVar RCV000888463, REVEL 0.37, ESM-1b 0.00, Benign/Likely benign, not provided; Acute intermittent porphyria
- S45W (p.Ser45Trp), gnomAD 11-119088681-C-G, REVEL 0.48, ESM-1b 1.00
- S45S (p.Ser45Ser), gnomAD 11-119088682-G-T, CADD 4.32
- P47S (p.Pro47Ser), TOPMed rs1226108681, gnomAD rs1226108681, REVEL 0.81, ESM-1b 0.65
- P47P (p.Pro47Pro), gnomAD 11-119088688-T-G, CADD 11.20
- G48A (p.Gly48Ala), gnomAD rs1279765868, REVEL 0.46, ESM-1b 0.00
- G48R (p.Gly48Arg), gnomAD 11-119088689-G-C, REVEL 0.55, ESM-1b 0.36
- G48G (p.Gly48Gly), rs767681753, gnomAD 11-119088691-C-A, CADD 11.50
- L49L (p.Leu49Leu), rs752790540, gnomAD 11-119088692-C-T, CADD 13.40
- L49Q (p.Leu49Gln), gnomAD 11-119088693-T-A, REVEL 0.76, ESM-1b 0.63
- Q50* (p.Gln50Ter), rs2134856747, ClinGen CA382888592, ClinVar RCV001389643, Ensembl rs2134856747, Pathogenic
- Q50P (p.Gln50Pro), rs765251645, ClinGen CA382888593, ClinVar RCV003386495, ESM-1b 1.00, AlphaMissense 0.08, Uncertain significance, Inborn genetic diseases
- Q50R (p.Gln50Arg), 1000Genomes rs765251645, ExAC rs765251645, gnomAD rs765251645, REVEL 0.41, ESM-1b 0.38, Uncertain significance, not provided
- Q50K (p.Gln50Lys), gnomAD 11-119088695-C-A, REVEL 0.42, ESM-1b 0.00
- Q50Q (p.Gln50Gln), rs1032690874, gnomAD 11-119088697-G-A, CADD 10.20
- F51S (p.Phe51Ser), gnomAD rs1178881026, REVEL 0.96, ESM-1b 1.00
- E52K (p.Glu52Lys), Ensembl rs11544979, REVEL 0.88, ESM-1b 1.00
- E52G (p.Glu52Gly), gnomAD 11-119088702-A-G, REVEL 0.95, ESM-1b 1.00
- I53V (p.Ile53Val), gnomAD rs1946152976, REVEL 0.72, ESM-1b 0.00
- I53I (p.Ile53Ile), gnomAD 11-119088706-C-T, CADD 16.30
- I54L (p.Ile54Leu), rs368061837, ClinGen CA6313920, ClinVar RCV000520884, ClinVar RCV001104610, REVEL 0.47, ESM-1b 0.00, Uncertain significance, not provided; Acute intermittent porphyria
- A55G (p.Ala55Gly), rs2497430462, ClinGen CA382889023, ClinVar RCV003683549, ESM-1b 0.00, AlphaMissense 0.13, Uncertain significance, not provided
- A55S (p.Ala55Ser), rs118204106, ClinGen CA251818, ClinVar RCV000001523, ClinVar RCV002272005, REVEL 0.64, ESM-1b 0.00, Uncertain significance, not specified; not provided
- M56T (p.Met56Thr), rs1946167378, ClinGen CA382889036, ClinVar RCV003050826, TOPMed rs1946167378, ESM-1b 1.00, AlphaMissense 0.90, Uncertain significance, not provided
- M56V (p.Met56Val), rs761130805, ClinGen CA6313955, NCI-TCGA Cosmic COSV5382, cosmic curated COSV53829, ESM-1b 1.00, AlphaMissense 0.31, Uncertain significance, not provided
- S57C (p.Ser57Cys), gnomAD rs1254756519, REVEL 0.75, ESM-1b 1.00
- T58S (p.Thr58Ser), gnomAD rs1946167675, REVEL 0.78, ESM-1b 1.00
- T59I (p.Thr59Ile), rs761004837, ClinGen CA6313956, ClinVar RCV002041322, UniProt VAR 074152, REVEL 0.54, ESM-1b 0.49, Uncertain significance, not provided
- D61N (p.Asp61Asn), UniProt VAR 011008, REVEL 0.83, ESM-1b 1.00, Pathogenic, in AIP
- D61Y (p.Asp61Tyr), rs2134859037, ClinGen CA382889248, ClinVar RCV002225205, UniProt VAR 025560, ESM-1b 1.00, AlphaMissense 0.92, Likely pathogenic, Acute intermittent porphyria
- K62E (p.Lys62Glu), rs2134859047, ClinGen CA382889274, ClinVar RCV001892228, Ensembl rs2134859047, ESM-1b 1.00, AlphaMissense 0.21, Uncertain significance, not provided
- K62N (p.Lys62Asn), rs1402435019, ClinGen CA382889292, ClinVar RCV001214092, ClinVar RCV001253215, REVEL 0.56, ESM-1b 1.00, Uncertain significance, not provided; Acute intermittent porphyria
- K62R (p.Lys62Arg), Ensembl rs2134859062, REVEL 0.76, ESM-1b 0.56
- L64F (p.Leu64Phe), NCI-TCGA Cosmic COSV5382, cosmic curated COSV53828, REVEL 0.77, ESM-1b 1.00, Uncertain significance, not provided
- D65H (p.Asp65His), rs368336004, ClinGen CA6313958, ClinVar RCV001340297, ESP rs368336004, ESM-1b 1.00, AlphaMissense 0.64, Uncertain significance, not provided
- A67T (p.Ala67Thr), cosmic curated COSV53829, gnomAD rs1487093855, REVEL 0.74, ESM-1b 1.00
- S69C (p.Ser69Cys), Ensembl rs1946168816, REVEL 0.83, ESM-1b 1.00
- S69P (p.Ser69Pro), TOPMed rs1249080912, ESM-1b 0.27, AlphaMissense 0.49
- K70* (p.Lys70Ter), rs1946168990, ClinGen CA1139662390, ClinVar RCV001210087, Pathogenic
- K70R (p.Lys70Arg), rs2134859281, ClinGen CA382889480, ClinVar RCV002028065, Ensembl rs2134859281, ESM-1b 1.00, AlphaMissense 0.12, Uncertain significance, not provided
- I71T (p.Ile71Thr), 1000Genomes rs149606894, ExAC rs149606894, gnomAD rs149606894, REVEL 0.91, ESM-1b 1.00
- G72E (p.Gly72Glu), gnomAD rs1946173573, REVEL 0.94, ESM-1b 1.00
- G72R (p.Gly72Arg), rs759414493, ClinGen CA6313981, ClinVar RCV002922536, ExAC rs759414493, REVEL 0.94, ESM-1b 1.00, Uncertain significance, not provided; not specified
- E73D (p.Glu73Asp), NCI-TCGA Cosmic COSV5382, cosmic curated COSV53827, REVEL 0.73, ESM-1b 0.00, Variant assessed as somatic; moderate impact.
- E73G (p.Glu73Gly), TOPMed rs1946173722, REVEL 0.75, ESM-1b 1.00
- S75A (p.Ser75Ala), NCI-TCGA TCGA novel, ESM-1b 0.00, AlphaMissense 0.33, Variant assessed as somatic; high impact.
- S75C (p.Ser75Cys), gnomAD rs1254014371, REVEL 0.96, ESM-1b 1.00
- S75N (p.Ser75Asn), rs767542253, ClinGen CA6313982, ClinVar RCV002019787, ExAC rs767542253, REVEL 0.68, ESM-1b 1.00, Uncertain significance, not provided
- S75R (p.Ser75Arg), NCI-TCGA Cosmic COSV5382, cosmic curated COSV53828, REVEL 0.97, ESM-1b 1.00, Variant assessed as somatic; moderate impact.
- T78P (p.Thr78Pro), UniProt VAR 025561, REVEL 0.97, ESM-1b 1.00, Pathogenic, in AIP
- T78S (p.Thr78Ser), rs1565754479, ClinGen CA382889813, ClinVar RCV001809124, Ensembl rs1565754479, REVEL 0.92, ESM-1b 1.00, Uncertain significance, Acute intermittent porphyria
- E80G (p.Glu80Gly), rs1946174360, ClinGen CA382889920, ClinVar RCV001054754, UniProt VAR 025562, ESM-1b 1.00, AlphaMissense 0.78, Likely pathogenic, not provided
- E80K (p.Glu80Lys), gnomAD rs1456465318, REVEL 0.96, ESM-1b 1.00
- L81F (p.Leu81Phe), rs1178276694, ClinGen CA382889957, cosmic curated COSV10512, ClinVar RCV003833758, REVEL 0.89, ESM-1b 1.00, Uncertain significance, not provided
- L81P (p.Leu81Pro), rs118204119, ClinGen CA251843, ClinVar RCV003764513, UniProt VAR 025563, ESM-1b 1.00, AlphaMissense 0.99, Pathogenic, Encephalopathy, porphyria-related
- E82Q (p.Glu82Gln), gnomAD rs1381220286, REVEL 0.94, ESM-1b 1.00
- H83N (p.His83Asn), Ensembl rs1946174660, ESM-1b 0.00, AlphaMissense 0.07
- H83R (p.His83Arg), rs1174451383, ClinGen CA382890011, ClinVar RCV002640148, gnomAD rs1174451383, ESM-1b 0.00, AlphaMissense 0.09, Uncertain significance, not provided
- A84D (p.Ala84Asp), UniProt VAR 089345, REVEL 0.85, ESM-1b 1.00, Pathogenic, Leukoencephalopathy, porphyria-related
- A84V (p.Ala84Val), TOPMed rs1946174844, gnomAD rs1946174844, REVEL 0.83, ESM-1b 1.00, Uncertain significance, not provided
- L85R (p.Leu85Arg), UniProt VAR 011009, REVEL 0.96, ESM-1b 1.00, Pathogenic, in AIP
- E86K (p.Glu86Lys), ExAC rs753502560, gnomAD rs753502560, REVEL 0.80, ESM-1b 0.81
- E86V (p.Glu86Val), rs150763621, ClinGen CA272879, ClinVar RCV000148510, ClinVar RCV001514054, REVEL 0.90, ESM-1b 0.27, Conflicting interpretations, Encephalopathy, porphyria-related; Acute intermittent porphyria; Leukoencephalop
- N88=, rs750889050, NCI-TCGA Cosmic COSV5383, Variant assessed as somatic; low impact.
- N88I (p.Asn88Ile), gnomAD rs1443863896, REVEL 0.90, ESM-1b 1.00
Public HMBS analysis runs
- HMBS analysis run — HMBS (556 variants) — completed 2026-05-30