Is FOXC1 p.Pro205fs (c.598_611dup) pathogenic?

FOXC1 p.Pro205fs (c.598611dup) is classified Pathogenic in FOXC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). Associated with Axenfeld-Rieger syndrome type 3.

What condition is associated with FOXC1 p.Pro205fs (c.598_611dup)?

FOXC1 p.Pro205fs (c.598_611dup) is associated with Axenfeld-Rieger syndrome type 3 (ClinVar).

FOXC1 p.Pro205fs

c.598_611dup · VCV3645220

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Axenfeld-Rieger syndrome type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 0.78, phastCons 1
Region caveats
Repeat context	tandem	GCCCCCGCCCGCGCCGCCA simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: FOXC1
Protein: p.Pro205fs
Coding: c.598_611dup
MANE Select: NM_001453
Type: Duplication
Location: chr6:1611038 (GRCh38)
Gene constraint: LOEUF 1.276 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.09
Residue 205: the 'disordered' region

Full FOXC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Axenfeld-Rieger syndrome type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FOXC1 p.Pro205Leu Uncertain significance ★ ⚠ same residue
FOXC1 p.Cys365fs Likely pathogenic ★★ same condition
FOXC1 p.Gln238fs Pathogenic ★★ same condition
FOXC1 p.Leu348fs Pathogenic/Likely pathogenic ★★ same condition
FOXC1 p.Ser276fs Pathogenic/Likely pathogenic ★★ same condition
FOXC1 p.386GAG[3] Uncertain significance ★★ same condition
FOXC1 p.Ala495_Gly496insAla Uncertain significance ★★ same condition
FOXC1 p.Ala326fs 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/foxc1-p-pro205fs (accessed [today's date]).

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