Is FOXG1 p.Pro110Arg (c.329C>G) pathogenic?

FOXG1 p.Pro110Arg (c.329C>G) is classified Conflicting classifications of pathogenicity in FOXG1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-07). AlphaMissense: likely benign (0.146); No allele count reported in gnomAD v4.1 (AN 1,256,788); Associated with FOXG1 disorder.

What condition is associated with FOXG1 p.Pro110Arg (c.329C>G)?

FOXG1 p.Pro110Arg (c.329C>G) is associated with FOXG1 disorder (ClinVar).

How common is FOXG1 p.Pro110Arg (c.329C>G) in the general population?

FOXG1 p.Pro110Arg (c.329C>G) is no allele count reported in gnomAD v4.1 (AN 1,256,788) (gnomAD).

What do computational predictors say about FOXG1 p.Pro110Arg (c.329C>G)?

AlphaMissense predicts likely benign (score 0.146) — an in-silico prediction, not a clinical call.

FOXG1 p.Pro110Arg

c.329C>G · rs2138660646 · VCV1215981

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.146 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,256,788)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FOXG1 disorder

Computational evidence

Protein change
AlphaMissense	0.146	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -14.24	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -1.3, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 505 bp · p 0.029 · regional, not allelic
Overall
CADD	20.9	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

No allele count reported in gnomAD v4.1 (AN 1,256,788). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FOXG1
Protein: p.Pro110Arg
Coding: c.329C>G
MANE Select: NM_005249
dbSNP: rs2138660646
Type: single nucleotide variant
Location: chr14:28767608 (GRCh38)
Gene constraint: LOEUF 0.36 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 58.79 · 1 PDB
Residue 110: 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.Pro110Ser Uncertain significance ★ ⚠ same residue
FOXG1 p.Pro110Gln Benign ★ ⚠ same residue
FOXG1 p.Pro110_Pro112del Uncertain significance ★ same residue
FOXG1 p.Pro110Thr 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

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-pro110arg (accessed [today's date]).

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