Is FOXF1 p.Pro110Ala (c.328C>G) pathogenic?

FOXF1 p.Pro110Ala (c.328C>G) is classified Uncertain significance in FOXF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-15). AlphaMissense: likely pathogenic (0.9872); Very rare (popmax 0.000424%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FOXF1 p.Pro110Ala (c.328C>G)?

FOXF1 p.Pro110Ala (c.328C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FOXF1 p.Pro110Ala (c.328C>G) in the general population?

FOXF1 p.Pro110Ala (c.328C>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about FOXF1 p.Pro110Ala (c.328C>G)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

FOXF1 p.Pro110Ala

c.328C>G · rs916878606 · VCV2357273

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic
REVEL	0.78	moderately pathogenic-leaning
SaProt	LLR -12.74	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 152 bp · p 1.1e-05 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000424% European (non-Finnish) · 5/1,180,036 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,613,828 alleles · very rare exomes 4/1,461,674 · genomes 1/152,154 · joint denominator

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.Pro110Ala
Coding: c.328C>G
MANE Select: NM_001451
dbSNP: rs916878606
Type: single nucleotide variant
Location: chr16:86510897 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.43 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.41
Residue 110: a DNA-binding 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.Met257Ile Uncertain significance ★★ ⚠ same condition
FOXF1 p.Pro11Gln Uncertain significance ★★ ⚠ same condition
FOXF1 p.Pro11Ser 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-pro110ala (accessed [today's date]).

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