Is FOXF1 p.Ser212= (c.636G>C) pathogenic?

FOXF1 p.Ser212= (c.636G>C) is classified Conflicting classifications of pathogenicity in FOXF1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-04). Very rare (popmax 0.00026%, nfe); Associated with alveolar capillary dysplasia with misalignment of pulmonary veins.

What condition is associated with FOXF1 p.Ser212= (c.636G>C)?

FOXF1 p.Ser212= (c.636G>C) is associated with alveolar capillary dysplasia with misalignment of pulmonary veins (ClinVar).

How common is FOXF1 p.Ser212= (c.636G>C) in the general population?

FOXF1 p.Ser212= (c.636G>C) is very rare (popmax 0.00026%, nfe) (gnomAD).

How is Congenital alveolar capillary dysplasia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

FOXF1 p.Ser212=

c.636G>C · rs776649998 · VCV689448

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00026%, nfe)

Conditions

alveolar capillary dysplasia with misalignment of pulmonary veins

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.098	GERP -3.9, phastCons 0.18
Overall
CADD	9.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00026% European (non-Finnish) · 3/1,155,622 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000214% 3/1,399,876 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FOXF1
Protein: p.Ser212=
Coding: c.636G>C
MANE Select: NM_001451
dbSNP: rs776649998
Type: single nucleotide variant
Location: chr16:86511205 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.43 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.41

Full FOXF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

alveolar capillary dysplasia with misalignment of pulmonary veins — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital alveolar capillary dysplasia (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Canada)

Similar variants

FOXF1 p.Gln90Ter Pathogenic ★★ same condition
FOXF1 p.Glu104Ter Pathogenic ★★ same condition
FOXF1 p.Leu56Val Likely pathogenic ★★ same condition
FOXF1 p.Ser223Ter Pathogenic ★★ same condition
FOXF1 p.His357Leu Uncertain significance ★★ ⚠ same condition
FOXF1 p.Met257Ile Uncertain significance ★★ ⚠ same condition
FOXF1 p.Ala323= Likely benign ★★ same condition
FOXF1 p.Gly361= Benign ★★ 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/foxf1-p-ser212 (accessed [today's date]).

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