Is FOXC1 p.Phe136fs (c.406_418del) pathogenic?

FOXC1 p.Phe136fs (c.406418del) is classified Likely pathogenic in FOXC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-01). No gnomAD frequency available for this variant.

How common is FOXC1 p.Phe136fs (c.406_418del) in the general population?

FOXC1 p.Phe136fs (c.406_418del) is no gnomAD frequency available for this variant (gnomAD).

FOXC1 p.Phe136fs

c.406_418del · rs2480502495 · VCV2578992

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 8.6	GERP 2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: FOXC1
Protein: p.Phe136fs
Coding: c.406_418del
MANE Select: NM_001453
dbSNP: rs2480502495
Type: Deletion
Location: chr6:1610847 (GRCh38)
Gene constraint: LOEUF 1.276 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.09
Residue 136: a DNA-binding region

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

Similar variants

FOXC1 p.Phe136Ser Likely pathogenic ★ same residue
FOXC1 p.Ala251fs Pathogenic/Likely pathogenic ★★ same type
FOXC1 p.Ala28fs Pathogenic/Likely pathogenic ★★ same type
FOXC1 p.Gln200fs Pathogenic ★★ same type
FOXC1 p.Ile223fs Pathogenic/Likely pathogenic ★★ same type
FOXC1 p.Leu168fs Pathogenic/Likely pathogenic ★★ same type
FOXC1 p.Leu240fs Pathogenic ★★ same type
FOXC1 p.Pro274fs Pathogenic/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/foxc1-p-phe136fs (accessed [today's date]).

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