FOXP2 (Forkhead box protein P2) variants and mutations
FOXP2 (also known as Forkhead box protein P2) is a human protein-coding gene encoding a forkhead box protein P2 protein. It controls gene networks required for development and plasticity of neural circuits involved in speech, language, and coordinated orofacial movements. Heterozygous pathogenic variants cause childhood apraxia of speech with variable language and motor abnormalities. This analysis covers 1,056 FOXP2 variants and mutations. Of these, 53% have computational variant effect predictions. Disease context includes childhood apraxia of speech, hereditary disease, and attention deficit-hyperactivity disorder. Example FOXP2 variants include M1?, M2I, and Q3P.
Variant analysis overview
- Gene: FOXP2
- Protein: Forkhead box protein P2
- UniProt accession: O15409
- Organism: Homo sapiens
- Variants analyzed: 1056
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 949 unspecified-consequence records; 45 synonymous variants; 55 missense variants; 2 splice-region variants; 1 stop lost; 1 stop-gained variants; 1 frameshift variants; 2 substitution
- Prediction scores: 555 variants have prediction scores (53% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: childhood apraxia of speech, hereditary disease, attention deficit-hyperactivity disorder, osteoarthritis, risk-taking behaviour, Pain, substance-related disorder, insomnia, post-traumatic stress disorder, Irritability, Neck pain, major depressive disorder.
Protein structure and variant hotspots
- Protein features: 1 domains.
- Structural context: 48 variants have structural context.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.
Notable FOXP2 variants
Examples include M1?, M2I, Q3P, Q3R, E4G, E4E, S5Y, A6G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10525, cosmic curated COSV63493
- M2I (p.Met2Ile), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- Q3P (p.Gln3Pro), Ensembl rs1188410790, REVEL 0.45, CADD 24.30
- Q3R (p.Gln3Arg), Ensembl rs1188410790
- E4G (p.Glu4Gly), rs1793857952, ClinGen CA369105505, ClinVar RCV001333763, Ensembl rs1793857952, Uncertain significance, Childhood apraxia of speech
- E4E (p.Glu4Glu), rs1207578096, gnomAD 7-114426523-A-G, CADD 11.10
- S5Y (p.Ser5Tyr), gnomAD rs1793858227, REVEL 0.68, CADD 25.30
- A6G (p.Ala6Gly), cosmic curated COSV10064
- A6V (p.Ala6Val), cosmic curated COSV63491, ExAC rs764109995, gnomAD rs764109995, REVEL 0.39, CADD 24.00
- A6P (p.Ala6Pro), gnomAD 7-114426527-G-C, REVEL 0.44, MetaLR 0.85
- A6A (p.Ala6Ala), rs751650034, gnomAD 7-114426529-G-A, CADD 11.80
- T7I (p.Thr7Ile), ESP rs377372067, ExAC rs377372067, TOPMed rs377372067, gnomAD rs377372067, REVEL 0.22, CADD 24.40
- T7P (p.Thr7Pro), ExAC rs757351650, gnomAD rs757351650, REVEL 0.26, CADD 25.60
- T7R (p.Thr7Arg), gnomAD 7-114426531-C-G, REVEL 0.20, MetaLR 0.82
- T7T (p.Thr7Thr), rs1207040670, gnomAD 7-114426532-A-G, CADD 11.60
- T9A (p.Thr9Ala), TOPMed rs1476956484, gnomAD rs1476956484, REVEL 0.21, CADD 23.60
- I10V (p.Ile10Val), gnomAD 7-114426539-A-G, REVEL 0.26, MetaLR 0.80
- N12I (p.Asn12Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N12S (p.Asn12Ser), TOPMed rs1273852421, REVEL 0.21, CADD 22.50
- N12N (p.Asn12Asn), rs963239607, gnomAD 7-114426547-C-T, CADD 9.87
- S13G (p.Ser13Gly), ExAC rs750736305, TOPMed rs750736305, gnomAD rs750736305, REVEL 0.13, CADD 23.00, Likely benign, Inborn genetic diseases
- S13N (p.Ser13Asn), ExAC rs756555227, gnomAD rs756555227, REVEL 0.12, CADD 24.50, Uncertain significance, Inborn genetic diseases
- S14P (p.Ser14Pro), gnomAD 7-114426551-T-C, REVEL 0.15, MetaLR 0.61
- S14L (p.Ser14Leu), gnomAD 7-114426552-C-T, REVEL 0.28, MetaLR 0.78
- S14S (p.Ser14Ser), gnomAD 7-114426553-A-G, CADD 12.20
- M15I (p.Met15Ile), gnomAD rs1386656928, REVEL 0.14, CADD 23.50
- M15V (p.Met15Val), ExAC rs770093841, gnomAD rs770093841, REVEL 0.24, CADD 19.90
- N16D (p.Asn16Asp), cosmic curated COSV10818, Ensembl rs1793860141
- N16K (p.Asn16Lys), cosmic curated COSV10887
- N16I (p.Asn16Ile), gnomAD 7-114426558-A-T, REVEL 0.11, MetaLR 0.64
- N16S (p.Asn16Ser), gnomAD 7-114426558-A-G, REVEL 0.06, MetaLR 0.57
- Q17L (p.Gln17Leu), rs201649896, ClinGen CA241662, cosmic curated COSV10441, ClinVar RCV000175859, REVEL 0.40, CADD 26.40, Conflicting interpretations, Inborn genetic diseases; not provided; Childhood apraxia of speech
- Q17R (p.Gln17Arg), gnomAD 7-114426561-A-G, REVEL 0.25, MetaLR 0.86
- N18D (p.Asn18Asp), rs763263115, ClinGen CA4445644, ClinVar RCV000319526, ClinVar RCV004022038, REVEL 0.24, CADD 25.80, Conflicting interpretations, not provided; Inborn genetic diseases; Childhood apraxia of speech
- N18N (p.Asn18Asn), gnomAD 7-114426565-T-C, CADD 10.80
- G19R (p.Gly19Arg), gnomAD 7-114426566-G-A, REVEL 0.67, MetaLR 0.97
- G19G (p.Gly19Gly), rs1330857790, gnomAD 7-114426568-A-C, CADD 12.20
- M20R (p.Met20Arg), TOPMed rs1793862053
- M20V (p.Met20Val), ExAC rs777361904, gnomAD rs777361904, REVEL 0.20, CADD 20.90
- M20I (p.Met20Ile), gnomAD 7-114426571-G-C, REVEL 0.21, MetaLR 0.66
- S21C (p.Ser21Cys), cosmic curated COSV63482
- S21N (p.Ser21Asn), ExAC rs746524111, TOPMed rs746524111, gnomAD rs746524111, REVEL 0.14, CADD 24.80
- T22N (p.Thr22Asn), NCI-TCGA TCGA novel, Ensembl rs2129205101, Variant assessed as somatic; moderate impact.
- T22P (p.Thr22Pro), gnomAD rs1793862344, REVEL 0.12, CADD 24.00
- T22S (p.Thr22Ser), gnomAD 7-114426575-A-T, REVEL 0.09, MetaLR 0.45
- T22A (p.Thr22Ala), gnomAD 7-114426575-A-G, REVEL 0.09, MetaLR 0.50
- T22T (p.Thr22Thr), rs770486674, gnomAD 7-114426577-T-G, CADD 10.60
- L23R (p.Leu23Arg), ExAC rs745618497, gnomAD rs745618497, REVEL 0.29, CADD 26.40
- L23L (p.Leu23Leu), rs769591194, gnomAD 7-114426580-A-G, CADD 9.99
- S24G (p.Ser24Gly), cosmic curated COSV10064, 1000Genomes rs181670107, ExAC rs181670107, TOPMed rs181670107, REVEL 0.14, CADD 24.50
- Q26Q (p.Gln26Gln), rs1288750878, gnomAD 7-114426589-A-G, CADD 9.88
- L27I (p.Leu27Ile), TOPMed rs1169006435
- D28A (p.Asp28Ala), ExAC rs762817913, gnomAD rs762817913, REVEL 0.13, CADD 24.40
- D28G (p.Asp28Gly), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- D28Y (p.Asp28Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D28D (p.Asp28Asp), rs768582806, gnomAD 7-114426595-T-C, CADD 10.60
- A29D (p.Ala29Asp), NCI-TCGA Cosmic COSV6348, NCI-TCGA Cosmic COSV6349, cosmic curated COSV63491, Variant assessed as somatic; moderate impact.
- A29G (p.Ala29Gly), TOPMed rs1793863638
- A29T (p.Ala29Thr), cosmic curated COSV63494
- A29V (p.Ala29Val), NCI-TCGA Cosmic COSV6348, cosmic curated COSV63483, NCI-TCGA Cosmic COSV6349, REVEL 0.23, CADD 23.70, Variant assessed as somatic; moderate impact.
- G30D (p.Gly30Asp), rs2485609220, ClinGen CA369105680, ClinVar RCV002376335, NCI-TCGA TCGA novel, Uncertain significance, Inborn genetic diseases
- G30G (p.Gly30Gly), gnomAD 7-114426601-C-A, CADD 10.60
- S31G (p.Ser31Gly), ExAC rs774408585, gnomAD rs774408585, REVEL 0.32, CADD 22.70
- S31N (p.Ser31Asn), ExAC rs762007110, gnomAD rs762007110, REVEL 0.20, CADD 25.80
- S31S (p.Ser31Ser), gnomAD 7-114426604-C-T, CADD 12.60
- R32G (p.Arg32Gly), gnomAD 7-114426605-A-G, REVEL 0.26, MetaLR 0.89
- R32R (p.Arg32Arg), gnomAD 7-114426605-A-C, CADD 12.40
- D33H (p.Asp33His), NCI-TCGA Cosmic COSV6349, Variant assessed as somatic; moderate impact.
- D33N (p.Asp33Asn), NCI-TCGA Cosmic COSV6349, cosmic curated COSV63490, Variant assessed as somatic; moderate impact.
- D33D (p.Asp33Asp), rs1362134492, gnomAD 7-114426610-T-C, CADD 11.50
- G34V (p.Gly34Val), gnomAD 7-114426612-G-T, REVEL 0.33, MetaLR 0.76
- G34E (p.Gly34Glu), gnomAD 7-114426612-G-A, REVEL 0.30, MetaLR 0.84
- R35I (p.Arg35Ile), NCI-TCGA Cosmic COSV6348, cosmic curated COSV63484, Variant assessed as somatic; moderate impact.
- R35K (p.Arg35Lys), cosmic curated COSV10610, NCI-TCGA Cosmic COSV6348, Variant assessed as somatic; moderate impact.
- R35S (p.Arg35Ser), TOPMed rs1793864416
- R35R (p.Arg35Arg), gnomAD 7-114426616-A-G, CADD 13.50
- S36P (p.Ser36Pro), rs750701057, ClinGen CA4445657, ClinVar RCV004394415, ClinVar RCV004784200, REVEL 0.10, CADD 22.80, Conflicting interpretations, Inborn genetic diseases; Childhood apraxia of speech
- S36S (p.Ser36Ser), gnomAD 7-114426619-A-T, CADD 12.60
- S37I (p.Ser37Ile), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- S37N (p.Ser37Asn), gnomAD rs1164029715, REVEL 0.16, CADD 23.60
- S37G (p.Ser37Gly), gnomAD 7-114426620-A-G, REVEL 0.08, MetaLR 0.61
- G38D (p.Gly38Asp), rs760842249, NCI-TCGA Cosmic COSV6349, cosmic curated COSV63490, ExAC rs760842249, REVEL 0.34, CADD 26.50, Variant assessed as somatic; moderate impact.
- D39Y (p.Asp39Tyr), cosmic curated COSV10740, gnomAD rs1423083583
- D39G (p.Asp39Gly), gnomAD 7-114426627-A-G, REVEL 0.25, MetaLR 0.81
- D39N (p.Asp39Asn), rs1584812023, gnomAD 7-114498886-G-A, CADD 11.60, SIFT 0.45
- D39D (p.Asp39Asp), rs1213870830, gnomAD 7-114498888-T-C, CADD 11.40
- T40I (p.Thr40Ile), 1000Genomes rs185960561, TOPMed rs185960561, gnomAD rs185960561, REVEL 0.24, CADD 23.20
- T40N (p.Thr40Asn), gnomAD 7-114426630-C-A, REVEL 0.21, MetaLR 0.86
- T40T (p.Thr40Thr), gnomAD 7-114426631-C-G, CADD 9.38
- S41G (p.Ser41Gly), ExAC rs766803095, gnomAD rs766803095
- S41N (p.Ser41Asn), NCI-TCGA Cosmic COSV6348, cosmic curated COSV63482, REVEL 0.15, CADD 22.30, Variant assessed as somatic; moderate impact.
- S41T (p.Ser41Thr), gnomAD 7-114426633-G-C, REVEL 0.14, MetaLR 0.68
- S41S (p.Ser41Ser), gnomAD 7-114426634-C-T, CADD 11.60
- S42C (p.Ser42Cys), rs754271344, ClinGen CA4445660, ClinVar RCV002430227, ClinVar RCV003408253, REVEL 0.09, CADD 25.20, Uncertain significance, FOXP2-related disorder; Inborn genetic diseases
- S42P (p.Ser42Pro), rs942638508, ClinGen CA165206973, ClinVar RCV001164489, gnomAD rs942638508, REVEL 0.15, CADD 25.30, Uncertain significance, Childhood apraxia of speech
- S42Y (p.Ser42Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S42T (p.Ser42Thr), gnomAD 7-114426635-T-A, REVEL 0.12, MetaLR 0.64
- S42S (p.Ser42Ser), gnomAD 7-114426637-T-C, CADD 7.98
- E43K (p.Glu43Lys), gnomAD rs1244944146, REVEL 0.26, CADD 29.20
- V44A (p.Val44Ala), rs1283187808, ClinGen CA369105771, ClinVar RCV001333765, gnomAD rs1283187808, Uncertain significance, Childhood apraxia of speech
- V44G (p.Val44Gly), gnomAD rs1283187808, REVEL 0.42, CADD 26.50, Uncertain significance
- S45N (p.Ser45Asn), ESP rs377588856, ExAC rs377588856, TOPMed rs377588856, gnomAD rs377588856
- S45T (p.Ser45Thr), ESP rs377588856, ExAC rs377588856, TOPMed rs377588856, gnomAD rs377588856, REVEL 0.27, CADD 23.80
- S45S (p.Ser45Ser), rs1206960236, gnomAD 7-114426646-C-T, CADD 14.10
- V47A (p.Val47Ala), rs1254975807, TOPMed rs1254975807, Variant assessed as somatic; moderate impact.
- V47I (p.Val47Ile), Ensembl rs1447075960, REVEL 0.24, CADD 23.80
- V47L (p.Val47Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V47V (p.Val47Val), rs1275071743, gnomAD 7-114426652-A-G, CADD 4.30
- E48* (p.Glu48Ter), NCI-TCGA Cosmic COSV6348, cosmic curated COSV63482, Variant assessed as somatic; high impact.
- E48G (p.Glu48Gly), gnomAD rs1202904573, REVEL 0.44, CADD 27.20
- E48K (p.Glu48Lys), ExAC rs779632352, gnomAD rs779632352, REVEL 0.27, CADD 27.40
- E48V (p.Glu48Val), rs1797440604, gnomAD 7-114498884-A-T, CADD 15.60, SIFT 0.50
- E48E (p.Glu48Glu), gnomAD 7-114498885-G-A, CADD 10.40
- L49V (p.Leu49Val), gnomAD 7-114426656-C-G, REVEL 0.25, MetaLR 0.91
- L49R (p.Leu49Arg), gnomAD 7-114426657-T-G, REVEL 0.44, MetaLR 0.90
- L50L (p.Leu50Leu), gnomAD 7-114426661-G-C, CADD 7.48
- H51P (p.His51Pro), cosmic curated COSV63483, TOPMed rs1793867473, gnomAD rs1793867473, REVEL 0.51, CADD 26.70
- H51Y (p.His51Tyr), NCI-TCGA TCGA novel, REVEL 0.39, CADD 25.40, Variant assessed as somatic; moderate impact.
- H51R (p.His51Arg), gnomAD 7-114426663-A-G, REVEL 0.49, MetaLR 0.83
- H51H (p.His51His), rs377158352, gnomAD 7-114570845-C-T, CADD 7.67
- L52L (p.Leu52Leu), rs1258244121, gnomAD 7-114426665-C-T, CADD 10.10
- Q54Q (p.Gln54Gln), rs1444157956, gnomAD 7-114426673-A-G, CADD 10.60
- Q55E (p.Gln55Glu), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; moderate impact.
- Q56R (p.Gln56Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A57T (p.Ala57Thr), ExAC rs748073993, TOPMed rs748073993, gnomAD rs748073993, REVEL 0.26, CADD 32.00
- A57A (p.Ala57Ala), rs1304678917, gnomAD 7-114534619-T-C, CADD 14.70
- L58R (p.Leu58Arg), NCI-TCGA Cosmic COSV6348, cosmic curated COSV63489, Variant assessed as somatic; moderate impact.
- L58P (p.Leu58Pro), gnomAD 7-114534621-T-C, REVEL 0.41, MetaLR 0.91
- L58L (p.Leu58Leu), rs771919689, gnomAD 7-114534622-C-T, CADD 4.30
- Q59H (p.Gln59His), NCI-TCGA Cosmic COSV6349, cosmic curated COSV63494, REVEL 0.24, CADD 21.10, Variant assessed as somatic; moderate impact.
- Q59R (p.Gln59Arg), cosmic curated COSV63492, REVEL 0.28, CADD 25.20
- A60E (p.Ala60Glu), Ensembl rs907456099
- A60T (p.Ala60Thr), cosmic curated COSV63492
- A60S (p.Ala60Ser), gnomAD 7-114534626-G-T, REVEL 0.21, MetaLR 0.77
- A60G (p.Ala60Gly), gnomAD 7-114534627-C-G, REVEL 0.23, MetaLR 0.77
- A60A (p.Ala60Ala), gnomAD 7-114534628-A-C, CADD 8.15
- A61S (p.Ala61Ser), gnomAD rs1452181228
- A61T (p.Ala61Thr), rs1452181228, NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, gnomAD rs1452181228, Variant assessed as somatic; moderate impact.
- A61A (p.Ala61Ala), rs747126499, gnomAD 7-114534631-A-C, CADD 6.08
- R62I (p.Arg62Ile), cosmic curated COSV63488
- R62G (p.Arg62Gly), gnomAD 7-114534632-A-G, REVEL 0.34, MetaLR 0.89
- R62R (p.Arg62Arg), rs771266770, gnomAD 7-114534634-A-G, CADD 10.90
- Q63H (p.Gln63His), TOPMed rs1357512652, gnomAD rs1357512652, REVEL 0.26, CADD 24.20
- Q63P (p.Gln63Pro), gnomAD 7-114498905-A-C, CADD 15.70, SIFT 0.30
- Q63L (p.Gln63Leu), rs1473867580, gnomAD 7-114498905-A-T, CADD 15.40, SIFT 0.69
- Q63Q (p.Gln63Gln), rs1357512652, gnomAD 7-114534637-A-G, CADD 8.74
- L64I (p.Leu64Ile), Ensembl rs1799289840
- L64L (p.Leu64Leu), gnomAD 7-114534640-T-A, CADD 8.89
- L65I (p.Leu65Ile), rs777042566, NCI-TCGA Cosmic COSV6349, cosmic curated COSV63494, ExAC rs777042566, REVEL 0.08, CADD 23.90, Uncertain significance, Inborn genetic diseases
- L65V (p.Leu65Val), gnomAD 7-114534641-C-G, REVEL 0.10, MetaLR 0.84
- L66* (p.Leu66Ter), rs1554412300, ClinGen CA369106016, ClinVar RCV000624216, Ensembl rs1554412300, Pathogenic
- Q67* (p.Gln67Ter), ExAC rs759949520, gnomAD rs759949520, CADD 36.00, Uncertain significance
- Q67E (p.Gln67Glu), rs759949520, ClinGen CA10622991, ClinVar RCV000279573, ExAC rs759949520, Uncertain significance, Childhood apraxia of speech
- Q67K (p.Gln67Lys), ExAC rs759949520, gnomAD rs759949520, Uncertain significance
- Q67R (p.Gln67Arg), ExAC rs765647678, TOPMed rs765647678, gnomAD rs765647678, REVEL 0.27, CADD 25.30
- Q67Q (p.Gln67Gln), rs1799290446, gnomAD 7-114534649-G-A, CADD 7.56
- Q68H (p.Gln68His), cosmic curated COSV63486
- Q68* (p.Gln68Ter), gnomAD 7-114534650-C-T, CADD 37.00
- Q68Q (p.Gln68Gln), gnomAD 7-114534652-G-A, CADD 8.03
- T70A (p.Thr70Ala), ExAC rs775730461, gnomAD rs775730461, REVEL 0.16, CADD 22.30
- T70I (p.Thr70Ile), rs1003299380, gnomAD 7-114498902-C-T, CADD 6.23, SIFT 0.54
- T70T (p.Thr70Thr), gnomAD 7-114498903-C-T, CADD 1.47
- T70S (p.Thr70Ser), gnomAD 7-114534656-A-T, REVEL 0.17, MetaLR 0.14
- S71G (p.Ser71Gly), gnomAD rs1237536573, REVEL 0.16, CADD 23.10
- S71N (p.Ser71Asn), Ensembl rs772294351
- S71R (p.Ser71Arg), gnomAD rs1237536573, REVEL 0.22, CADD 24.80
- S71P (p.Ser71Pro), rs1797441386, gnomAD 7-114498895-T-C, CADD 12.10, SIFT 0.32
- S71F (p.Ser71Phe), rs1020633052, gnomAD 7-114498896-C-T, CADD 12.70, SIFT 0.35
- S71S (p.Ser71Ser), rs966830549, gnomAD 7-114498897-T-C, CADD 14.90
- G72* (p.Gly72Ter), NCI-TCGA Cosmic COSV1006, cosmic curated COSV10064, Variant assessed as somatic; high impact.
- G72G (p.Gly72Gly), rs1460518283, gnomAD 7-114534664-A-G, CADD 12.80
- G72D (p.Gly72Asp), rs1801263903, gnomAD 7-114570841-G-A, CADD 22.80, SIFT 0.18
- G72A (p.Gly72Ala), gnomAD 7-114570841-G-C, CADD 16.50, SIFT 1.00
- G72R (p.Gly72Arg), rs781352228, gnomAD 7-114570852-G-C, CADD 23.10, SIFT 0.01
- G72S (p.Gly72Ser), rs781352228, gnomAD 7-114570852-G-A, CADD 20.90, SIFT 0.10
- L73M (p.Leu73Met), cosmic curated COSV10466
- L73L (p.Leu73Leu), rs1181346217, gnomAD 7-114534665-T-C, CADD 8.16
- L73W (p.Leu73Trp), gnomAD 7-114534666-T-G, REVEL 0.30, MetaLR 0.85
- K74R (p.Lys74Arg), Ensembl rs1448096881
- K74K (p.Lys74Lys), rs1249532997, gnomAD 7-114534670-A-G, CADD 8.37
Public FOXP2 analysis runs
- FOXP2 analysis run — FOXP2 (1,056 variants) — completed 2026-08-19