Is FOXG1 p.Pro63= (c.189G>T) pathogenic?

FOXG1 p.Pro63= (c.189G>T) is classified Benign/Likely benign in FOXG1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-03-27). Ultra-rare (popmax 0.0137%, sas); Associated with FOXG1 disorder.

What condition is associated with FOXG1 p.Pro63= (c.189G>T)?

FOXG1 p.Pro63= (c.189G>T) is associated with FOXG1 disorder (ClinVar).

How common is FOXG1 p.Pro63= (c.189G>T) in the general population?

FOXG1 p.Pro63= (c.189G>T) is ultra-rare (popmax 0.0137%, sas) (gnomAD).

FOXG1 p.Pro63=

c.189G>T · rs796052451 · VCV205467

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, sas)

Conditions

FOXG1 disorder

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 1.9	GERP 0.085, phastCons 1
Overall
CADD	10.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0137% South Asian · 6/43,802 alleles

Filtering AF 0.0059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00402%

Overall 0.00079% 9/1,139,784 alleles · ultra-rare exomes 7/1,001,978 · genomes 2/137,806 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0137%	7,300
African / African-American	0.00516%	19,397

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.Pro63=
Coding: c.189G>T
MANE Select: NM_005249
dbSNP: rs796052451
Type: single nucleotide variant
Location: chr14:28767468 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.79 · 1 PDB
Residue 63: the 'disordered' region

Full FOXG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FOXG1 disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For FOXG1 syndrome (Orphanet):

Onset: Neonatal

Similar variants

FOXG1 p.Pro63Arg Likely benign ★★ ⚠ same residue
FOXG1 p.Pro63Gln Uncertain significance ★ ⚠ same residue
FOXG1 p.Pro63Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
FOXG1 p.Pro63fs Pathogenic ★★★ same residue
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

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-pro63 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown