# NM_001451.2(FOXF1):c.(?_15)_(*58_?)del

https://sugi.bio/variant/foxf1-c-15

## Summary

**FOXF1 c.(?_15** is classified **Pathogenic** in FOXF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-10-26). Associated with Idiopathic and/or familial pulmonary arterial hypertension.

**At a glance:** Pathogenic · review: Single submitter · 1 submitter · 1 linked condition

## For patients & families {#patients}

This is a change in the FOXF1 gene that is reported as disease-causing, but on limited review, submitted by 1 submitter, and is linked to Idiopathic and/or familial pulmonary arterial hypertension.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [FOXF1](https://sugi.bio/atlas/gene/FOXF1/) |
| Coding change (HGVS c.) | c.(?_15 |
| MANE Select transcript | [NM_001451](https://www.ncbi.nlm.nih.gov/nuccore/NM_001451) |
| Variant type | Deletion |
| Location | chr16:None-None (GRCh38) |
| ClinVar | [VCV228348](https://www.ncbi.nlm.nih.gov/clinvar/variation/228348/) |

**All HGVS expressions:** `NC_000016.10:g.(?_86510584)_(86513143_?)del`, `NC_000016.9:g.(?_86544190)_(86546749_?)del`, `NM_001451.2:c.(?_15)_(*58_?)del`

## Gene constraint & dosage {#gene-context}

**FOXF1** population constraint: LOEUF 0.685, pLI 0.427, missense-Z 0.30525; ClinGen dosage — haploinsufficiency 3/3, triplosensitivity 0/3. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 59.41, 21% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of FOXF1 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** FOXF1's established molecular role includes RNA polymerase II transcription regulatory region sequence-specific DNA binding.


### Pathways affected {#pathways}

FOXF1 participates in **2 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Formation of lateral plate mesoderm](https://reactome.org/content/detail/R-HSA-9758920) | electronic |
| [Regulation of CDH11 gene transcription](https://reactome.org/content/detail/R-HSA-9762293) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** RNA polymerase II transcription regulatory region sequence-specific DNA binding, DNA-binding transcription activator activity, RNA polymerase II-specific, DNA binding.

**Biological process:** blood vessel development, in utero embryonic development, morphogenesis of a branching structure, endocardial cushion development, cardiac left ventricle morphogenesis, midgut development.

## Clinical significance {#significance}

**Pathogenic** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2015-10-26.

**Submitter consensus:** unanimous (1/1 Pathogenic).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Pathogenic | criteria provided, single submitter | clinical testing | 2015-10-26 |

## Associated conditions {#conditions}

[Idiopathic and/or familial pulmonary arterial hypertension](https://sugi.bio/atlas/disease/idiopathic-and-or-familial-pulmonary-arterial-hypertension/).

**Reported phenotype names (ClinVar):** Idiopathic and/or familial pulmonary arterial hypertension.

## Similar variants {#similar}

Related FOXF1 variant pages (same residue, condition, or type): [FOXF1 p.Leu300fs](/variant/foxf1-p-leu300fs), [FOXF1 c.*1176del](/variant/foxf1-c-star-1176del), [FOXF1 p.Ala268fs](/variant/foxf1-p-ala268fs), [FOXF1 p.Ala297fs](/variant/foxf1-p-ala297fs), [FOXF1 p.Asn317fs](/variant/foxf1-p-asn317fs), [FOXF1 p.Cys148fs](/variant/foxf1-p-cys148fs), [FOXF1 p.Gly281fs](/variant/foxf1-p-gly281fs), [FOXF1 p.Leu314fs](/variant/foxf1-p-leu314fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 228348). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*