FOXG1 (Forkhead box protein G1) variants and mutations
FOXG1 (also known as Forkhead box protein G1) is a human protein-coding gene encoding a forkhead box protein G1 protein. It controls forebrain progenitor proliferation, neuronal differentiation, and cortical patterning during embryonic development. Haploinsufficiency or dysregulating variants cause FOXG1 syndrome, characterized by severe developmental impairment, absent or limited speech, abnormal movements, and frequent epilepsy. This analysis covers 1,212 FOXG1 variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes FOXG1 disorder, Rett syndrome, and hereditary disease. Example FOXG1 variants include M1?, M1L, and L2M.
Variant analysis overview
- Gene: FOXG1
- Protein: Forkhead box protein G1
- UniProt accession: P55316
- Organism: Homo sapiens
- Variants analyzed: 1212
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 759 unspecified-consequence records; 79 synonymous variants; 277 missense variants; 41 frameshift variants; 8 stop-gained variants; 30 in-frame deletions; 8 in-frame insertions; 11 substitution
- Prediction scores: 932 variants have prediction scores (77% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: FOXG1 disorder, Rett syndrome, hereditary disease, neurodevelopmental disorder, mathematical ability, undetermined early-onset epileptic encephalopathy, atypical Rett syndrome, placenta praevia, Strabismus, Abnormality of the nervous system, Global developmental delay, schizophrenia.
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 FOXG1 variants
Examples include M1?, M1L, L2M, L2L, L2V, L2P, D3A, D3E. 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), rs1168923100, ClinGen CA389474152, ClinVar RCV001876562, ClinVar RCV005628920, MetaLR 0.75, MetaSVM 0.16, Uncertain significance, not provided; FOXG1 disorder
- L2M (p.Leu2Met), ExAC rs776244220, TOPMed rs776244220, gnomAD rs776244220, REVEL 0.36, CADD 23.20
- L2L (p.Leu2Leu), rs776244220, gnomAD 14-28767283-C-T, CADD 11.30
- L2V (p.Leu2Val), gnomAD 14-28767283-C-G, REVEL 0.36, MetaLR 0.83
- L2P (p.Leu2Pro), gnomAD 14-28767284-T-C, REVEL 0.44, MetaLR 0.82
- D3A (p.Asp3Ala), ExAC rs761420014, gnomAD rs761420014, REVEL 0.51, CADD 23.30
- D3E (p.Asp3Glu), ExAC rs764914165, gnomAD rs764914165, REVEL 0.33, CADD 22.10, Likely benign
- D3V (p.Asp3Val), ExAC rs761420014, gnomAD rs761420014, REVEL 0.75, CADD 24.70
- D3T (p.Asp3Thr), gnomAD 14-28767284-TG-T, CADD 25.70
- D3Y (p.Asp3Tyr), gnomAD 14-28767286-G-T, REVEL 0.69, MetaLR 0.90
- D3N (p.Asp3Asn), gnomAD 14-28767286-G-A, REVEL 0.45, MetaLR 0.85
- D3H (p.Asp3His), gnomAD 14-28767286-G-C, REVEL 0.54, MetaLR 0.90
- D3G (p.Asp3Gly), gnomAD 14-28767287-A-G, REVEL 0.56, MetaLR 0.84
- D3D (p.Asp3Asp), rs764914165, gnomAD 14-28767288-C-T, CADD 12.20
- M4L (p.Met4Leu), gnomAD rs1466463571, REVEL 0.40, CADD 22.40, Uncertain significance
- M4V (p.Met4Val), gnomAD rs1466463571, REVEL 0.44, CADD 21.90, Uncertain significance, not provided
- M4K (p.Met4Lys), gnomAD 14-28767290-T-A, REVEL 0.56, MetaLR 0.76
- M4R (p.Met4Arg), gnomAD 14-28767290-T-G, REVEL 0.65, MetaLR 0.75
- M4T (p.Met4Thr), gnomAD 14-28767290-T-C, REVEL 0.64, MetaLR 0.73
- M4I (p.Met4Ile), gnomAD 14-28767291-G-C, REVEL 0.48, MetaLR 0.77
- G5* (p.Gly5Ter), NCI-TCGA Cosmic COSV1004, Ensembl rs2138659880, CADD 34.00, Variant assessed as somatic; high impact.
- G5V (p.Gly5Val), gnomAD rs1333660434, REVEL 0.59, CADD 23.90
- G5E (p.Gly5Glu), gnomAD 14-28767290-TG-T, CADD 25.60
- G5R (p.Gly5Arg), gnomAD 14-28767292-G-A, REVEL 0.62, MetaLR 0.82
- G5G (p.Gly5Gly), gnomAD 14-28767294-A-G, CADD 12.50
- D6E (p.Asp6Glu), TOPMed rs1394571667, gnomAD rs1394571667, REVEL 0.13, CADD 13.20
- D6N (p.Asp6Asn), NCI-TCGA TCGA novel, REVEL 0.25, CADD 23.10, Variant assessed as somatic; moderate impact.
- D6Y (p.Asp6Tyr), gnomAD 14-28767295-G-T, REVEL 0.48, MetaLR 0.69
- D6G (p.Asp6Gly), gnomAD 14-28767296-A-G, REVEL 0.25, MetaLR 0.66
- D6V (p.Asp6Val), gnomAD 14-28767296-A-T, REVEL 0.38, MetaLR 0.66
- D6D (p.Asp6Asp), rs1394571667, gnomAD 14-28767297-T-C, CADD 11.30
- R7K (p.Arg7Lys), Ensembl rs2138659891, REVEL 0.39, CADD 22.00
- R7G (p.Arg7Gly), gnomAD 14-28767298-A-G, REVEL 0.47, MetaLR 0.67
- R7W (p.Arg7Trp), gnomAD 14-28767298-A-T, REVEL 0.64, MetaLR 0.81
- R7M (p.Arg7Met), gnomAD 14-28767299-G-T, REVEL 0.63, MetaLR 0.82
- R7T (p.Arg7Thr), gnomAD 14-28767299-G-C, REVEL 0.41, MetaLR 0.64
- R7S (p.Arg7Ser), gnomAD 14-28767300-G-T, REVEL 0.36, MetaLR 0.67
- R7R (p.Arg7Arg), rs1881772109, gnomAD 14-28767300-G-A, CADD 13.00
- K8E (p.Lys8Glu), Ensembl rs2138659897, REVEL 0.40, CADD 22.40
- K8Q (p.Lys8Gln), gnomAD 14-28767301-A-C, REVEL 0.41, MetaLR 0.76
- K8* (p.Lys8Ter), gnomAD 14-28767301-A-T, CADD 34.00
- K8R (p.Lys8Arg), gnomAD 14-28767302-A-G, REVEL 0.42, MetaLR 0.74
- K8K (p.Lys8Lys), gnomAD 14-28767303-A-G, CADD 13.50
- K8N (p.Lys8Asn), gnomAD 14-28767303-A-C, REVEL 0.39, MetaLR 0.72
- E9A (p.Glu9Ala), ExAC rs772990946, gnomAD rs772990946, REVEL 0.06, CADD 23.10
- E9K (p.Glu9Lys), gnomAD rs1390986068, REVEL 0.09, CADD 23.40
- E9Q (p.Glu9Gln), NCI-TCGA Cosmic COSV5739, Variant assessed as somatic; moderate impact.
- E9R (p.Glu9Arg), gnomAD 14-28767300-GA-G, CADD 23.70
- E9* (p.Glu9Ter), gnomAD 14-28767304-G-T, CADD 35.00
- E9V (p.Glu9Val), gnomAD 14-28767305-A-T, REVEL 0.09, MetaLR 0.07
- E9G (p.Glu9Gly), gnomAD 14-28767305-A-G, REVEL 0.06, MetaLR 0.08
- E9D (p.Glu9Asp), gnomAD 14-28767306-G-T, REVEL 0.07, MetaLR 0.08
- E9E (p.Glu9Glu), rs762567782, gnomAD 14-28767306-G-A, CADD 12.00
- V10A (p.Val10Ala), Ensembl rs1881772519, REVEL 0.09, CADD 23.10, Uncertain significance, FOXG1 disorder
- V10L (p.Val10Leu), gnomAD rs1235342890, REVEL 0.08, CADD 22.80, Uncertain significance
- V10M (p.Val10Met), rs1235342890, gnomAD rs1235342890, REVEL 0.10, CADD 23.30, Conflicting interpretations, FOXG1 disorder
- V10E (p.Val10Glu), gnomAD 14-28767308-T-A, REVEL 0.22, MetaLR 0.06
- V10V (p.Val10Val), gnomAD 14-28767309-G-T, CADD 11.80
- K11* (p.Lys11Ter), Ensembl rs1555321166
- K11N (p.Lys11Asn), Ensembl rs1566444810, REVEL 0.08, CADD 23.40
- K11E (p.Lys11Glu), gnomAD 14-28767310-A-G, REVEL 0.14, MetaLR 0.08
- K11R (p.Lys11Arg), gnomAD 14-28767311-A-G, REVEL 0.10, MetaLR 0.10
- K11K (p.Lys11Lys), gnomAD 14-28767312-A-G, CADD 14.10
- M12N (p.Met12Asn), gnomAD 14-28767309-G-GA, CADD 27.30
- M12* (p.Met12Ter), rs1281283259, gnomAD 14-28767309-GA-G, CADD 26.40
- M12L (p.Met12Leu), gnomAD 14-28767313-A-T, REVEL 0.10, MetaLR 0.08
- M12V (p.Met12Val), gnomAD 14-28767313-A-G, REVEL 0.08, MetaLR 0.09
- M12T (p.Met12Thr), gnomAD 14-28767314-T-C, REVEL 0.11, MetaLR 0.08
- M12I (p.Met12Ile), gnomAD 14-28767315-G-T, REVEL 0.17, MetaLR 0.09
- I13F (p.Ile13Phe), gnomAD 14-28767316-A-T, REVEL 0.15, MetaLR 0.09
- I13V (p.Ile13Val), gnomAD 14-28767316-A-G, REVEL 0.15, MetaLR 0.09
- I13L (p.Ile13Leu), gnomAD 14-28767316-A-C, REVEL 0.12, MetaLR 0.08
- I13T (p.Ile13Thr), gnomAD 14-28767317-T-C, REVEL 0.09, MetaLR 0.10
- I13N (p.Ile13Asn), gnomAD 14-28767317-T-A, REVEL 0.09, MetaLR 0.09
- I13I (p.Ile13Ile), rs1322636276, gnomAD 14-28767318-C-T, CADD 13.40
- I13M (p.Ile13Met), gnomAD 14-28767318-C-G, REVEL 0.06, MetaLR 0.08
- P14S (p.Pro14Ser), rs2502223421, ClinGen CA389474246, ClinVar RCV003021436, REVEL 0.10, CADD 22.60, Uncertain significance, FOXG1 disorder
- P14T (p.Pro14Thr), gnomAD 14-28767319-C-A, REVEL 0.09, MetaLR 0.10
- P14H (p.Pro14His), gnomAD 14-28767320-C-A, REVEL 0.12, MetaLR 0.08
- P14L (p.Pro14Leu), gnomAD 14-28767320-C-T, REVEL 0.13, MetaLR 0.09
- P14P (p.Pro14Pro), rs1199009034, gnomAD 14-28767321-C-T, CADD 14.10
- K15T (p.Lys15Thr), gnomAD rs1259645564, REVEL 0.15, CADD 23.30
- K15S (p.Lys15Ser), gnomAD 14-28767317-TC-T, CADD 24.80
- K15E (p.Lys15Glu), gnomAD 14-28767322-A-G, REVEL 0.10, MetaLR 0.11
- K15* (p.Lys15Ter), gnomAD 14-28767322-A-T, CADD 35.00
- K15M (p.Lys15Met), gnomAD 14-28767323-A-T, REVEL 0.13, MetaLR 0.12
- K15R (p.Lys15Arg), gnomAD 14-28767323-A-G, REVEL 0.10, MetaLR 0.12
- K15K (p.Lys15Lys), gnomAD 14-28767324-G-A, CADD 12.80
- K15N (p.Lys15Asn), gnomAD 14-28767324-G-C, REVEL 0.09, MetaLR 0.10
- S16P (p.Ser16Pro), rs1881773666, ClinGen CA389474259, ClinVar RCV003629541, TOPMed rs1881773666, REVEL 0.18, CADD 23.30, Uncertain significance, FOXG1 disorder
- S16T (p.Ser16Thr), gnomAD 14-28767325-T-A, REVEL 0.08, MetaLR 0.11
- S16F (p.Ser16Phe), gnomAD 14-28767326-C-T, REVEL 0.15, MetaLR 0.14
- S16C (p.Ser16Cys), gnomAD 14-28767326-C-G, REVEL 0.15, MetaLR 0.15
- S16Y (p.Ser16Tyr), gnomAD 14-28767326-C-A, REVEL 0.15, MetaLR 0.14
- S16S (p.Ser16Ser), gnomAD 14-28767327-C-T, CADD 13.50
- S17P (p.Ser17Pro), gnomAD 14-28767328-T-C, REVEL 0.23, MetaLR 0.11
- S17* (p.Ser17Ter), gnomAD 14-28767329-C-A, CADD 35.00
- S17L (p.Ser17Leu), gnomAD 14-28767329-C-T, REVEL 0.19, MetaLR 0.11
- S17S (p.Ser17Ser), gnomAD 14-28767330-G-T, CADD 13.30
- F18L (p.Phe18Leu), gnomAD 14-28767331-T-C, REVEL 0.14, MetaLR 0.10
- F18S (p.Phe18Ser), gnomAD 14-28767332-T-C, REVEL 0.21, MetaLR 0.10
- F18F (p.Phe18Phe), rs766174892, gnomAD 14-28767333-C-T, CADD 13.00
- S19N (p.Ser19Asn), TOPMed rs1176748250, gnomAD rs1176748250, REVEL 0.10, CADD 23.00
- S19C (p.Ser19Cys), gnomAD 14-28767334-A-T, REVEL 0.21, MetaLR 0.15
- S19R (p.Ser19Arg), gnomAD 14-28767334-A-C, REVEL 0.23, MetaLR 0.10
- S19G (p.Ser19Gly), gnomAD 14-28767334-A-G, REVEL 0.08, MetaLR 0.08
- S19I (p.Ser19Ile), gnomAD 14-28767335-G-T, REVEL 0.22, MetaLR 0.09
- S19T (p.Ser19Thr), gnomAD 14-28767335-G-C, REVEL 0.11, MetaLR 0.07
- S19S (p.Ser19Ser), rs372915038, gnomAD 14-28767336-C-T, CADD 13.50
- I20F (p.Ile20Phe), gnomAD 14-28767337-A-T, REVEL 0.18, MetaLR 0.10
- I20V (p.Ile20Val), gnomAD 14-28767337-A-G, REVEL 0.10, MetaLR 0.08
- I20T (p.Ile20Thr), gnomAD 14-28767338-T-C, REVEL 0.24, MetaLR 0.08
- I20N (p.Ile20Asn), gnomAD 14-28767338-T-A, REVEL 0.23, MetaLR 0.09
- I20I (p.Ile20Ile), gnomAD 14-28767339-C-T, CADD 13.20
- N21T (p.Asn21Thr), gnomAD 14-28767339-CA-C, CADD 26.00
- N21D (p.Asn21Asp), gnomAD 14-28767340-A-G, REVEL 0.11, MetaLR 0.10
- N21S (p.Asn21Ser), gnomAD 14-28767341-A-G, REVEL 0.09, MetaLR 0.10
- N21K (p.Asn21Lys), gnomAD 14-28767342-C-G, REVEL 0.13, MetaLR 0.11
- N21N (p.Asn21Asn), gnomAD 14-28767342-C-T, CADD 11.90
- S22G (p.Ser22Gly), gnomAD 14-28767343-A-G, REVEL 0.08, MetaLR 0.09
- S22N (p.Ser22Asn), gnomAD 14-28767344-G-A, REVEL 0.22, MetaLR 0.07
- S22T (p.Ser22Thr), gnomAD 14-28767344-G-C, REVEL 0.19, MetaLR 0.08
- S22I (p.Ser22Ile), gnomAD 14-28767344-G-T, REVEL 0.19, MetaLR 0.10
- S22S (p.Ser22Ser), gnomAD 14-28767345-C-T, CADD 13.40
- S22R (p.Ser22Arg), gnomAD 14-28767345-C-A, REVEL 0.08, MetaLR 0.10
- L23M (p.Leu23Met), gnomAD 14-28767346-C-A, REVEL 0.09, MetaLR 0.10
- L23L (p.Leu23Leu), gnomAD 14-28767346-C-T, CADD 12.00
- L23R (p.Leu23Arg), gnomAD 14-28767347-T-G, REVEL 0.19, MetaLR 0.08
- L23P (p.Leu23Pro), gnomAD 14-28767347-T-C, REVEL 0.21, MetaLR 0.09
- L23Q (p.Leu23Gln), gnomAD 14-28767347-T-A, REVEL 0.15, MetaLR 0.08
- V24C (p.Val24Cys), gnomAD 14-28767347-TG-T, CADD 26.00
- V24M (p.Val24Met), gnomAD 14-28767349-G-A, REVEL 0.08, MetaLR 0.09
- V24L (p.Val24Leu), gnomAD 14-28767349-G-T, REVEL 0.06, MetaLR 0.07
- V24E (p.Val24Glu), gnomAD 14-28767350-T-A, REVEL 0.26, MetaLR 0.09
- V24A (p.Val24Ala), gnomAD 14-28767350-T-C, REVEL 0.13, MetaLR 0.08
- V24V (p.Val24Val), gnomAD 14-28767351-G-T, CADD 10.50
- P25H (p.Pro25His), Ensembl rs1555321170, REVEL 0.19, CADD 24.10
- P25T (p.Pro25Thr), gnomAD 14-28767352-C-A, REVEL 0.21, MetaLR 0.17
- P25A (p.Pro25Ala), gnomAD 14-28767352-C-G, REVEL 0.17, MetaLR 0.16
- P25S (p.Pro25Ser), gnomAD 14-28767352-C-T, REVEL 0.14, MetaLR 0.17
- P25R (p.Pro25Arg), gnomAD 14-28767353-C-G, REVEL 0.21, MetaLR 0.16
- P25L (p.Pro25Leu), gnomAD 14-28767353-C-T, REVEL 0.20, MetaLR 0.16
- P25P (p.Pro25Pro), rs1434342683, gnomAD 14-28767354-C-G, CADD 9.56
- E26R (p.Glu26Arg), gnomAD 14-28767351-GC-G, CADD 25.30
- E26* (p.Glu26Ter), gnomAD 14-28767355-G-T, CADD 35.00
- E26K (p.Glu26Lys), gnomAD 14-28767355-G-A, REVEL 0.22, MetaLR 0.18
- E26G (p.Glu26Gly), gnomAD 14-28767356-A-G, REVEL 0.22, MetaLR 0.21
- E26V (p.Glu26Val), gnomAD 14-28767356-A-T, REVEL 0.26, MetaLR 0.22
- E26D (p.Glu26Asp), gnomAD 14-28767357-G-T, REVEL 0.15, MetaLR 0.14
- E26E (p.Glu26Glu), rs2138659953, gnomAD 14-28767357-G-A, CADD 10.50
- A27G (p.Ala27Gly), TOPMed rs1344440643, gnomAD rs1344440643, REVEL 0.11, CADD 24.40
- A27T (p.Ala27Thr), NCI-TCGA Cosmic COSV5739, REVEL 0.15, CADD 23.30, Variant assessed as somatic; moderate impact.
- A27V (p.Ala27Val), TOPMed rs1344440643, gnomAD rs1344440643, REVEL 0.15, CADD 24.40
- A27S (p.Ala27Ser), gnomAD 14-28767358-G-T, REVEL 0.15, MetaLR 0.16
- A27E (p.Ala27Glu), gnomAD 14-28767359-C-A, REVEL 0.22, MetaLR 0.17
- A27A (p.Ala27Ala), rs1199178172, gnomAD 14-28767360-G-A, CADD 13.30
- V28F (p.Val28Phe), gnomAD 14-28767361-G-T, REVEL 0.18, MetaLR 0.11
- V28I (p.Val28Ile), gnomAD 14-28767361-G-A, REVEL 0.12, MetaLR 0.08
- V28A (p.Val28Ala), gnomAD 14-28767362-T-C, REVEL 0.06, MetaLR 0.08
- V28D (p.Val28Asp), gnomAD 14-28767362-T-A, REVEL 0.24, MetaLR 0.10
- V28V (p.Val28Val), gnomAD 14-28767363-C-T, CADD 11.80
- Q29* (p.Gln29Ter), rs2502223575, ClinGen CA389474348, ClinVar RCV002292885, CADD 35.00, Pathogenic
- Q29R (p.Gln29Arg), rs1594382746, gnomAD 14-28767362-TC-T, CADD 24.80
- Q29K (p.Gln29Lys), gnomAD 14-28767364-C-A, REVEL 0.10, MetaLR 0.09
- Q29E (p.Gln29Glu), gnomAD 14-28767364-C-G, REVEL 0.07, MetaLR 0.09
- Q29L (p.Gln29Leu), gnomAD 14-28767365-A-T, REVEL 0.13, MetaLR 0.11
- Q29H (p.Gln29His), gnomAD 14-28767366-G-T, REVEL 0.03, MetaLR 0.08
- Q29Q (p.Gln29Gln), rs1881774420, gnomAD 14-28767366-G-A, CADD 10.60
- N30S (p.Asn30Ser), gnomAD rs1053995886, REVEL 0.06, CADD 15.70
- N30R (p.Asn30Arg), gnomAD 14-28767364-CAG-C, CADD 25.40
- N30D (p.Asn30Asp), gnomAD 14-28767367-A-G, REVEL 0.08, MetaLR 0.08
- N30T (p.Asn30Thr), gnomAD 14-28767368-A-C, REVEL 0.08, MetaLR 0.08
- N30N (p.Asn30Asn), rs1254598069, gnomAD 14-28767369-C-T, CADD 11.30
- N30K (p.Asn30Lys), gnomAD 14-28767369-C-A, REVEL 0.07, MetaLR 0.08
- D31G (p.Asp31Gly), gnomAD rs1881774689, REVEL 0.09, CADD 23.10
- D31N (p.Asp31Asn), rs2138659978, ClinGen CA389474361, ClinVar RCV001732582, Ensembl rs2138659978, REVEL 0.18, CADD 23.50, Likely benign, not provided
- D31H (p.Asp31His), gnomAD 14-28767370-G-C, REVEL 0.10, MetaLR 0.14
- D31Y (p.Asp31Tyr), gnomAD 14-28767370-G-T, REVEL 0.20, MetaLR 0.13
- D31E (p.Asp31Glu), gnomAD 14-28767371-AC-A, CADD 24.50
Public FOXG1 analysis runs
- FOXG1 analysis run — FOXG1 (1,212 variants) — completed 2026-08-21