FOXG1 p.Pro66=
c.198G>A · rs2502224264 · VCV3250892
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00543%, eas)
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 0.063 | GERP -0.96, phastCons 0.84 |
| Overall | ||
| CADD | 10.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00543%
East Asian · 1/18,406 alleles
Filtering AF
8.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.5e-05%
Overall
0.000528%
6/1,136,588 alleles · very rare
exomes 6/993,336 · genomes 0/143,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00543% | 18,406 |
| Remaining individualsnot grpmax-eligible | 0.00536% | 18,667 |
| European (non-Finnish) | 0.000333% | 300,072 |
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.Pro66=
- Coding
- c.198G>A
- MANE Select
- NM_005249
- dbSNP
- rs2502224264
- Type
- single nucleotide variant
- Location
- chr14:28767477 (GRCh38)
- Gene constraint
- LOEUF 0.36 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 58.79 · 1 PDB
- Residue 66
- the 'disordered' region
Similar variants
- FOXG1 p.Pro66Leu Uncertain significance ★ ⚠ same residue
- FOXG1 p.Pro66Thr Uncertain significance ★ ⚠ same residue
- FOXG1 p.Pro66Ala Likely benign ★ ⚠ same residue
- FOXG1 p.Arg230Leu Likely pathogenic ★★★ same type
- FOXG1 p.Asn187Lys Pathogenic ★★★ same type
- FOXG1 p.Asn236Asp Likely pathogenic ★★★ same type
- FOXG1 p.Gly224Ser Likely pathogenic ★★★ same type
- FOXG1 p.Gly250Ser Likely pathogenic ★★★ same type
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-pro66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown