Is FOXG1 p.Arg201Pro (c.602G>C) pathogenic?

FOXG1 p.Arg201Pro (c.602G>C) is classified Pathogenic/Likely pathogenic in FOXG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-13). AlphaMissense: likely pathogenic (0.9998); Absent from gnomAD v4.1; Associated with FOXG1 disorder.

What condition is associated with FOXG1 p.Arg201Pro (c.602G>C)?

FOXG1 p.Arg201Pro (c.602G>C) is associated with FOXG1 disorder (ClinVar).

How common is FOXG1 p.Arg201Pro (c.602G>C) in the general population?

FOXG1 p.Arg201Pro (c.602G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FOXG1 p.Arg201Pro (c.602G>C)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

FOXG1 p.Arg201Pro

c.602G>C · rs2138661213 · VCV1332866

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FOXG1 disorder

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic ✓ concordant with ClinVar
REVEL	0.822	moderately pathogenic-leaning
SaProt	LLR -17.08	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP -0.65, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 66 bp · p 9e-09 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FOXG1
Protein: p.Arg201Pro
Coding: c.602G>C
MANE Select: NM_005249
dbSNP: rs2138661213
Type: single nucleotide variant
Location: chr14:28767881 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.79 · 1 PDB
Residue 201: a DNA-binding 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.Arg201Leu Likely pathogenic ★ same residue
FOXG1 p.Arg201= Likely benign ★ same residue
FOXG1 p.Arg201Gln Uncertain significance ★ ⚠ 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
FOXG1 p.Gly250Ser 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-arg201pro (accessed [today's date]).

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