Is FOXF1 p.Pro11Ser (c.31C>T) pathogenic?

FOXF1 p.Pro11Ser (c.31C>T) is classified Uncertain significance in FOXF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-25). AlphaMissense: likely benign (0.0509); Ultra-rare (popmax 0.0781%, afr); Associated with Inborn genetic diseases.

What condition is associated with FOXF1 p.Pro11Ser (c.31C>T)?

FOXF1 p.Pro11Ser (c.31C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FOXF1 p.Pro11Ser (c.31C>T) in the general population?

FOXF1 p.Pro11Ser (c.31C>T) is ultra-rare (popmax 0.0781%, afr) (gnomAD).

What do computational predictors say about FOXF1 p.Pro11Ser (c.31C>T)?

AlphaMissense predicts likely benign (score 0.0509) — an in-silico prediction, not a clinical call.

FOXF1 p.Pro11Ser

c.31C>T · VCV3279578

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0509 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0781%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0509	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 142 bp · p 0.74 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0781% African / African-American · 51/65,296 alleles

Filtering AF 0.061% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0549%

Overall 0.00439% 61/1,390,016 alleles · ultra-rare exomes 29/1,238,294 · genomes 32/151,722 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0781%	1,280
Admixed American	0.0146%	6,865
Remaining individualsnot grpmax-eligible	0.00759%	13,180
European (non-Finnish)	0.000185%	540,570

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.Pro11Ser
Coding: c.31C>T
MANE Select: NM_001451
Type: single nucleotide variant
Location: chr16:86510600 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.43 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.41
Residue 11: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FOXF1 p.Pro11Gln Uncertain significance ★★ ⚠ same residue
FOXF1 p.Met257Ile Uncertain significance ★★ ⚠ same condition
FOXF1 p.Pro110Ala Uncertain significance ★★ ⚠ same condition
FOXF1 p.Pro182Leu Uncertain significance ★★ ⚠ same condition
FOXF1 p.Pro33Leu Uncertain significance ★★ ⚠ same condition
FOXF1 p.Pro5Leu Uncertain significance ★★ ⚠ same condition
FOXF1 p.Ala245Pro Uncertain significance ★ ⚠ same condition
FOXF1 p.Ala24Thr Uncertain significance ★ ⚠ 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-pro11ser (accessed [today's date]).

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