MITF (O75030) variants and mutations
MITF (also known as O75030) is a human protein-coding gene encoding a microphthalmia-associated transcription factor protein. Its annotated function is transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis. It is annotated at the nucleus. This analysis covers 1,314 MITF variants and mutations. Of these, 50% have computational variant effect predictions. Disease context includes Waardenburg syndrome type 2A, Tietz syndrome, and coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness. Example MITF variants include M1?, M1L, and M1T.
Variant analysis overview
- Gene: MITF
- Protein: O75030
- UniProt accession: O75030
- Organism: Homo sapiens
- Variants analyzed: 1314
- Variant scope: all variants
- Completed: 2026-08-28
Variant and mutation evidence
- Variant composition: 1,146 unspecified-consequence records; 119 missense variants; 29 synonymous variants; 9 frameshift variants; 8 stop-gained variants; 2 splice-region variants; 1 in-frame deletions
- Prediction scores: 661 variants have prediction scores (50% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Waardenburg syndrome type 2A, Tietz syndrome, coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness, melanoma, cutaneous malignant, susceptibility to, 8, Waardenburg syndrome, cutaneous melanoma, Waardenburg syndrome type 2, hair color, MITF-related melanoma and renal cell carcinoma predisposition syndrome, Tietze syndrome, melanoma, Rare genetic deafness.
Protein structure and variant hotspots
- Protein features: 1 domains; 7 post-translational modification sites.
- Structural context: 104 variants have structural context.
- PTM context: 18 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, MaveDB, LitVar.
Notable MITF variants
Examples include M1?, M1L, M1T, M1K, M1I, Q2*, Q2E, Q2K. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- M1L (p.Met1Leu), rs1182582559, gnomAD 3-69794508-A-T, CADD 0.42
- M1T (p.Met1Thr), rs150321715, gnomAD 3-69794509-T-C, CADD 9.87
- M1K (p.Met1Lys), rs150321715, gnomAD 3-69794509-T-A, CADD 9.38
- M1I (p.Met1Ile), gnomAD 3-69866314-G-A, CADD 19.80
- Q2* (p.Gln2Ter), Ensembl rs2106732376, CADD 37.00
- Q2E (p.Gln2Glu), gnomAD 3-69739601-C-G, REVEL 0.21, CADD 25.90
- Q2K (p.Gln2Lys), gnomAD 3-69739601-C-A, REVEL 0.19, CADD 24.60
- Q2R (p.Gln2Arg), gnomAD 3-69739602-A-G, REVEL 0.26, CADD 24.70
- Q2H (p.Gln2His), gnomAD 3-69739603-G-T, REVEL 0.15, CADD 26.90
- Q2Q (p.Gln2Gln), gnomAD 3-69739603-G-A, CADD 13.70
- Q2L (p.Gln2Leu), gnomAD 3-69866310-A-T, CADD 20.40
- S3C (p.Ser3Cys), gnomAD rs1269737529
- S3T (p.Ser3Thr), gnomAD 3-69739604-T-A, REVEL 0.09, CADD 21.40
- S3Y (p.Ser3Tyr), gnomAD 3-69739605-C-A, REVEL 0.07, CADD 24.20
- S3F (p.Ser3Phe), gnomAD 3-69739605-C-T, REVEL 0.07, CADD 23.50
- S3S (p.Ser3Ser), gnomAD 3-69739606-C-A, CADD 8.82
- E4* (p.Glu4Ter), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10072, CADD 38.00, Variant assessed as somatic; high impact.
- E4K (p.Glu4Lys), TOPMed rs1703448556, REVEL 0.22, CADD 26.60
- E4N (p.Glu4Asn), gnomAD 3-69739606-CG-C, CADD 32.00
- E4V (p.Glu4Val), gnomAD 3-69739608-A-T, REVEL 0.23, CADD 31.00
- E4Q (p.Glu4Gln), gnomAD 3-69763854-G-C, CADD 14.60
- E4G (p.Glu4Gly), gnomAD 3-69763855-A-G, CADD 14.50
- E4E (p.Glu4Glu), rs546125344, gnomAD 3-69763856-A-G, CADD 12.00
- E4D (p.Glu4Asp), gnomAD 3-69866296-G-T, CADD 18.70
- S5* (p.Ser5Ter), TOPMed rs1413689457, gnomAD rs1413689457, CADD 37.00
- S5A (p.Ser5Ala), Ensembl rs2106732413
- S5L (p.Ser5Leu), cosmic curated COSV10888, TOPMed rs1413689457, gnomAD rs1413689457, REVEL 0.24, CADD 29.80
- S5W (p.Ser5Trp), TOPMed rs1413689457, gnomAD rs1413689457, REVEL 0.22, CADD 31.00
- S5T (p.Ser5Thr), gnomAD 3-69739610-T-A, REVEL 0.12, CADD 28.20
- S5S (p.Ser5Ser), gnomAD 3-69739612-G-T, CADD 9.87
- S5F (p.Ser5Phe), rs371867296, gnomAD 3-69866328-C-T, CADD 19.50
- S5G (p.Ser5Gly), rs1198181906, gnomAD 3-69866336-A-G, CADD 20.70
- G6E (p.Gly6Glu), gnomAD rs1246900531, REVEL 0.35, CADD 28.30
- G6R (p.Gly6Arg), TOPMed rs1207755717, gnomAD rs1207755717, REVEL 0.29, CADD 25.40
- G6W (p.Gly6Trp), gnomAD 3-69739613-G-T, REVEL 0.38, CADD 32.00
- G6V (p.Gly6Val), gnomAD 3-69739614-G-T, REVEL 0.34, CADD 28.60
- G6G (p.Gly6Gly), rs767644021, gnomAD 3-69739615-G-T, CADD 11.30
- G6* (p.Gly6Ter), gnomAD 3-69763845-G-T, CADD 12.60
- G6A (p.Gly6Ala), gnomAD 3-69763846-G-C, CADD 11.50
- I7V (p.Ile7Val), gnomAD 3-69739616-A-G, REVEL 0.16, CADD 26.90
- I7I (p.Ile7Ile), rs2106732481, gnomAD 3-69739618-C-T, CADD 12.10
- I7F (p.Ile7Phe), gnomAD 3-69763884-A-T, CADD 0.01
- I7N (p.Ile7Asn), gnomAD 3-69763885-T-A, CADD 2.22
- I7T (p.Ile7Thr), rs773317681, gnomAD 3-69794476-T-C, CADD 2.72
- V8M (p.Val8Met), gnomAD rs1188943383, REVEL 0.24, CADD 24.80
- V8L (p.Val8Leu), gnomAD 3-69739619-G-C, REVEL 0.26, CADD 24.40
- V8A (p.Val8Ala), gnomAD 3-69739620-T-C, REVEL 0.22, CADD 24.80
- V8V (p.Val8Val), rs968258324, gnomAD 3-69739621-G-A, CADD 14.30
- V8E (p.Val8Glu), gnomAD 3-69763867-T-A, CADD 10.40
- V8I (p.Val8Ile), gnomAD 3-69763869-G-A, CADD 8.46
- V8F (p.Val8Phe), rs2062248402, gnomAD 3-69763869-G-T, CADD 8.01
- V8G (p.Val8Gly), rs1245506680, gnomAD 3-69866307-T-G, CADD 20.80
- P9A (p.Pro9Ala), TOPMed rs979674711, gnomAD rs979674711, REVEL 0.09, CADD 17.40
- P9R (p.Pro9Arg), cosmic curated COSV10526, ESP rs371372825, TOPMed rs371372825
- P9S (p.Pro9Ser), gnomAD 3-69739622-C-T, REVEL 0.07, CADD 23.70
- P9T (p.Pro9Thr), gnomAD 3-69739622-C-A, REVEL 0.07, CADD 23.40
- P9Q (p.Pro9Gln), gnomAD 3-69739623-C-A, REVEL 0.11, CADD 27.60
- P9L (p.Pro9Leu), gnomAD 3-69739623-C-T, REVEL 0.17, CADD 24.60
- P9P (p.Pro9Pro), rs2106732530, gnomAD 3-69739624-G-A, CADD 14.70
- D10N (p.Asp10Asn), gnomAD 3-69739625-G-A, REVEL 0.21, CADD 32.00
- D10Y (p.Asp10Tyr), gnomAD 3-69739625-G-T, REVEL 0.37, CADD 32.00
- D10G (p.Asp10Gly), gnomAD 3-69739626-A-G, REVEL 0.41, CADD 32.00
- F11L (p.Phe11Leu), Ensembl rs2106732545, REVEL 0.23, CADD 25.80
- F11S (p.Phe11Ser), Ensembl rs2106732537, REVEL 0.28, CADD 32.00
- F11Y (p.Phe11Tyr), gnomAD 3-69739629-T-A, REVEL 0.18, CADD 29.40
- F11F (p.Phe11Phe), gnomAD 3-69739630-C-T, CADD 14.90
- E12D (p.Glu12Asp), cosmic curated COSV61476, ExAC rs750693668, gnomAD rs750693668, REVEL 0.11, CADD 23.00
- E12* (p.Glu12Ter), gnomAD 3-69739631-G-T, CADD 38.00
- E12K (p.Glu12Lys), gnomAD 3-69739631-G-A, REVEL 0.17, CADD 26.20
- E12G (p.Glu12Gly), gnomAD 3-69739632-A-G, REVEL 0.21, CADD 26.00
- V13A (p.Val13Ala), cosmic curated COSV10590, ExAC rs780389752, TOPMed rs780389752, gnomAD rs780389752, REVEL 0.15, CADD 24.80, Uncertain significance, Tietz syndrome; Melanoma, cutaneous malignant, susceptibility to, 8; Waardenburg
- V13G (p.Val13Gly), ExAC rs780389752, TOPMed rs780389752, gnomAD rs780389752, Uncertain significance
- V13I (p.Val13Ile), gnomAD rs1420140107, REVEL 0.14, CADD 24.50
- V13F (p.Val13Phe), gnomAD 3-69739634-G-T, REVEL 0.25, CADD 25.60
- V13D (p.Val13Asp), gnomAD 3-69739635-T-A, REVEL 0.25, CADD 30.00
- V13V (p.Val13Val), rs938160478, gnomAD 3-69739636-C-A, CADD 13.70
- G14E (p.Gly14Glu), NCI-TCGA TCGA novel, REVEL 0.37, CADD 22.30, Variant assessed as somatic; moderate impact.
- G14R (p.Gly14Arg), 1000Genomes rs202028114, ExAC rs202028114, gnomAD rs202028114, REVEL 0.34, CADD 24.10
- G14W (p.Gly14Trp), gnomAD 3-69739637-G-T, REVEL 0.34, CADD 32.00
- G14V (p.Gly14Val), gnomAD 3-69739638-G-T, REVEL 0.35, CADD 24.70
- G14G (p.Gly14Gly), gnomAD 3-69739639-G-T, CADD 13.50
- E15* (p.Glu15Ter), TOPMed rs1038868097, gnomAD rs1038868097, CADD 38.00
- E15G (p.Glu15Gly), ExAC rs758114521, gnomAD rs758114521, REVEL 0.15, CADD 24.30
- E15Q (p.Glu15Gln), TOPMed rs1038868097, gnomAD rs1038868097, REVEL 0.14, CADD 23.70
- E15R (p.Glu15Arg), rs2106732605, gnomAD 3-69739636-CG-C, CADD 32.00
- E15K (p.Glu15Lys), gnomAD 3-69739640-G-A, REVEL 0.20, CADD 24.20
- E15D (p.Glu15Asp), gnomAD 3-69739642-G-T, REVEL 0.06, CADD 21.70
- E15E (p.Glu15Glu), rs777833130, gnomAD 3-69739642-G-A, CADD 14.00
- E16Q (p.Glu16Gln), gnomAD rs1292958607, REVEL 0.12, CADD 22.90
- E16E (p.Glu16Glu), rs746864722, gnomAD 3-69739645-G-A, CADD 14.50
- E16D (p.Glu16Asp), gnomAD 3-69739645-G-T, REVEL 0.16, CADD 22.40
- F17C (p.Phe17Cys), Ensembl rs2106732665
- F17V (p.Phe17Val), gnomAD 3-69739646-T-G, REVEL 0.18, CADD 23.40
- F17S (p.Phe17Ser), gnomAD 3-69763884-AT-A, CADD 0.59
- F17I (p.Phe17Ile), gnomAD 3-69763887-T-A, CADD 6.74
- F17L (p.Phe17Leu), rs1441101806, gnomAD 3-69763889-C-G, CADD 4.54
- F17F (p.Phe17Phe), gnomAD 3-69763889-C-T, CADD 5.03
- H18N (p.His18Asn), cosmic curated COSV10590, 1000Genomes rs201296271, REVEL 0.12, CADD 22.70
- H18R (p.His18Arg), NCI-TCGA TCGA novel, REVEL 0.13, CADD 22.80, Variant assessed as somatic; moderate impact.
- H18Y (p.His18Tyr), gnomAD 3-69739649-C-T, REVEL 0.14, CADD 21.90
- H18D (p.His18Asp), gnomAD 3-69739649-C-G, REVEL 0.21, CADD 23.00
- H18H (p.His18His), rs898626089, gnomAD 3-69739651-T-C, CADD 13.20
- H18Q (p.His18Gln), gnomAD 3-69739651-T-A, REVEL 0.26, CADD 18.00
- E19A (p.Glu19Ala), 1000Genomes rs191483142, TOPMed rs191483142, gnomAD rs191483142, REVEL 0.28, CADD 23.30
- E19K (p.Glu19Lys), TOPMed rs1703450453, REVEL 0.20, CADD 23.90
- E19* (p.Glu19Ter), gnomAD 3-69739652-G-T, CADD 39.00
- E19G (p.Glu19Gly), gnomAD 3-69739653-A-G, REVEL 0.21, CADD 24.00
- E19D (p.Glu19Asp), gnomAD 3-69739654-A-T, REVEL 0.10, CADD 21.80
- E20D (p.Glu20Asp), rs780642512, ClinGen CA2490169, ClinVar RCV000602256, ExAC rs780642512, REVEL 0.32, CADD 19.30, Uncertain significance, not specified
- E20K (p.Glu20Lys), ExAC rs770451570, TOPMed rs770451570, gnomAD rs770451570, REVEL 0.32, CADD 26.20
- E20* (p.Glu20Ter), gnomAD 3-69739655-G-T, CADD 39.00
- E20E (p.Glu20Glu), gnomAD 3-69739657-G-A, CADD 14.30
- E20Q (p.Glu20Gln), gnomAD 3-69763899-G-C, CADD 3.01
- E20G (p.Glu20Gly), gnomAD 3-69763900-A-G, CADD 0.06
- E20V (p.Glu20Val), rs1478378726, gnomAD 3-69763900-A-T, CADD 0.05
- P21S (p.Pro21Ser), Ensembl rs2106732731, REVEL 0.20, CADD 22.50
- P21T (p.Pro21Thr), Ensembl rs2106732731, REVEL 0.19, CADD 22.80
- P21R (p.Pro21Arg), gnomAD 3-69739659-C-G, REVEL 0.23, CADD 24.40
- P21H (p.Pro21His), gnomAD 3-69739659-C-A, REVEL 0.22, CADD 24.60
- P21L (p.Pro21Leu), gnomAD 3-69739659-C-T, REVEL 0.18, CADD 24.50
- P21P (p.Pro21Pro), gnomAD 3-69739660-C-T, CADD 15.60
- K22E (p.Lys22Glu), rs1323075294, ClinGen CA353558827, ClinVar RCV003947227, REVEL 0.30, CADD 23.70, Uncertain significance, MITF-related disorder
- K22Q (p.Lys22Gln), TOPMed rs1323075294, gnomAD rs1323075294, REVEL 0.16, CADD 29.30
- K22I (p.Lys22Ile), gnomAD 3-69739662-A-T, REVEL 0.27, CADD 32.00
- K22K (p.Lys22Lys), gnomAD 3-69739663-A-G, CADD 15.30
- K22R (p.Lys22Arg), rs2106811262, gnomAD 3-69763899-GA-G, CADD 0.01
- K22M (p.Lys22Met), gnomAD 3-69763903-A-T, CADD 7.58
- K22N (p.Lys22Asn), gnomAD 3-69763904-G-T, CADD 6.29
- T23I (p.Thr23Ile), TOPMed rs1703451048, REVEL 0.23, CADD 23.00
- T23A (p.Thr23Ala), gnomAD 3-69739664-A-G, REVEL 0.29, CADD 23.20
- T23S (p.Thr23Ser), gnomAD 3-69739665-C-G, REVEL 0.23, CADD 21.90
- T23N (p.Thr23Asn), gnomAD 3-69739665-C-A, REVEL 0.22, CADD 22.80
- T23T (p.Thr23Thr), rs745352985, gnomAD 3-69739666-C-T, CADD 15.10
- T23P (p.Thr23Pro), gnomAD 3-69763905-GA-G, CADD 2.85
- Y24* (p.Tyr24Ter), Ensembl rs2106732767
- Y24C (p.Tyr24Cys), Ensembl rs1559601708, REVEL 0.35, CADD 25.70
- Y24Y (p.Tyr24Tyr), gnomAD 3-69739669-T-C, CADD 14.00
- Y24H (p.Tyr24His), gnomAD 3-69866342-T-C, CADD 19.20
- Y24F (p.Tyr24Phe), rs202166652, gnomAD 3-69866343-A-T, CADD 16.10
- Y25C (p.Tyr25Cys), Ensembl rs1559601716, REVEL 0.35, CADD 31.00
- Y25H (p.Tyr25His), gnomAD 3-69739670-T-C, REVEL 0.27, CADD 30.00
- Y25S (p.Tyr25Ser), gnomAD 3-69739671-A-C, REVEL 0.40, CADD 25.90
- Y25F (p.Tyr25Phe), gnomAD 3-69739671-A-T, REVEL 0.19, CADD 24.90
- Y25Y (p.Tyr25Tyr), gnomAD 3-69739672-C-T, CADD 13.30
- Y25* (p.Tyr25Ter), gnomAD 3-69739672-C-A, CADD 36.00
- E26* (p.Glu26Ter), TOPMed rs1264298203, gnomAD rs1264298203, CADD 39.00
- E26K (p.Glu26Lys), TOPMed rs1264298203, gnomAD rs1264298203, REVEL 0.26, CADD 26.40
- E26G (p.Glu26Gly), gnomAD 3-69739674-A-G, REVEL 0.29, CADD 26.10
- E26E (p.Glu26Glu), rs1703451970, gnomAD 3-69739675-A-G, CADD 15.50
- L27I (p.Leu27Ile), gnomAD 3-69739676-C-A, REVEL 0.12, CADD 22.40
- L27H (p.Leu27His), gnomAD 3-69739677-T-A, REVEL 0.33, CADD 32.00
- L27L (p.Leu27Leu), gnomAD 3-69739678-C-T, CADD 15.00
- L27F (p.Leu27Phe), rs1428971222, gnomAD 3-69763851-C-T, CADD 13.20
- L27P (p.Leu27Pro), gnomAD 3-69763852-T-C, CADD 15.80
- L27V (p.Leu27Val), rs1466374667, gnomAD 3-69763893-C-G, CADD 0.01
- L27S (p.Leu27Ser), gnomAD 3-69763918-T-C, CADD 6.58
- L27* (p.Leu27Ter), gnomAD 3-69763918-T-A, CADD 6.07
- L27M (p.Leu27Met), gnomAD 3-69763923-C-A, CADD 2.49
- L27R (p.Leu27Arg), rs2107228215, gnomAD 3-69866301-T-G, CADD 20.50
- K28* (p.Lys28Ter), gnomAD rs1483686343, CADD 38.00
- K28N (p.Lys28Asn), Ensembl rs1703452110
- K28E (p.Lys28Glu), gnomAD 3-69739679-A-G, REVEL 0.26, CADD 25.40
- K28R (p.Lys28Arg), gnomAD 3-69739680-A-G, REVEL 0.21, CADD 25.10
- S29G (p.Ser29Gly), NCI-TCGA TCGA novel, REVEL 0.20, CADD 25.30, Variant assessed as somatic; moderate impact.
- S29I (p.Ser29Ile), TOPMed rs1703452239, REVEL 0.39, CADD 32.00
- S29V (p.Ser29Val), gnomAD 3-69739678-CA-C, CADD 32.00
- S29C (p.Ser29Cys), gnomAD 3-69739682-A-T, REVEL 0.26, CADD 32.00
- S29N (p.Ser29Asn), gnomAD 3-69739683-G-A, REVEL 0.17, CADD 31.00
- Q30H (p.Gln30His), Ensembl rs2106732844, REVEL 0.12, CADD 23.10
- Q30R (p.Gln30Arg), TOPMed rs1346042841, REVEL 0.26, CADD 25.40
- Q30K (p.Gln30Lys), gnomAD 3-69739685-C-A, REVEL 0.20, CADD 24.60
- Q30Q (p.Gln30Gln), gnomAD 3-69739687-A-G, CADD 13.10
- P31R (p.Pro31Arg), Ensembl rs1559601734, REVEL 0.24, CADD 24.70
- P31S (p.Pro31Ser), gnomAD 3-69739688-C-T, REVEL 0.19, CADD 24.70
- P31T (p.Pro31Thr), gnomAD 3-69739688-C-A, REVEL 0.21, CADD 24.60
- P31L (p.Pro31Leu), gnomAD 3-69739689-C-T, REVEL 0.15, CADD 25.30
- P31Q (p.Pro31Gln), gnomAD 3-69739689-C-A, REVEL 0.17, CADD 27.50
- P31P (p.Pro31Pro), rs2106732861, gnomAD 3-69739690-G-A, CADD 9.57
- L32P (p.Leu32Pro), ExAC rs769488240, gnomAD rs769488240, REVEL 0.28, CADD 27.00
Public MITF analysis runs
- MITF analysis run — MITF (1,314 variants) — completed 2026-08-28