FOXG1 p.Pro67=
c.201G>T · rs587780944 · VCV137388
ClinGen expert panel — Rett and Angelman-like Disorders VCEP
Benign for FOXG1 disorder. Applied ACMG criteria (verbatim):
BP7 BA1
Curation rationale (ClinGen, verbatim)
The allele frequency of the p.Pro67= variant in FOXG1 is 0.055% in European (Non-Finnish) sub population in gnomAD, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The silent p.Pro67= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Pro67= variant in FOXG1 is classified as benign based on the ACMG/AMP criteria (BA1, BP7).
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.71 | GERP 0.028, phastCons 1 |
| Overall | ||
| CADD | 11.47 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0769% | 1,300 |
| Remaining individualsnot grpmax-eligible | 0.0592% | 1,690 |
| Finnishnot grpmax-eligible | 0.0415% | 2,412 |
| African / African-American | 0.0183% | 5,474 |
| Admixed American | 0.00603% | 16,585 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- FOXG1
- Protein
- p.Pro67=
- Coding
- c.201G>T
- MANE Select
- NM_005249
- dbSNP
- rs587780944
- Type
- single nucleotide variant
- Location
- chr14:28767480 (GRCh38)
- Gene constraint
- LOEUF 0.36 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.79 · 1 PDB
- Residue 67
- the 'disordered' region
Disease context
FOXG1 disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor FOXG1 syndrome (Orphanet):
- Onset
- Neonatal
Similar variants
- FOXG1 p.Arg230Leu Likely pathogenic ★★★ same condition
- FOXG1 p.Asn187Lys Pathogenic ★★★ same condition
- FOXG1 p.Asn236Asp Likely pathogenic ★★★ same condition
- FOXG1 p.Gly224Ser Likely pathogenic ★★★ same condition
- FOXG1 p.Gly250Ser Likely pathogenic ★★★ same condition
- FOXG1 p.Gly267Ser Pathogenic ★★★ same condition
- FOXG1 p.Ile207Thr Likely pathogenic ★★★ same condition
- FOXG1 p.Ile229Leu Likely pathogenic ★★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/foxg1-p-pro67 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown