Is FOXF1 p.Arg86Pro (c.257G>C) pathogenic?

FOXF1 p.Arg86Pro (c.257G>C) is classified Pathogenic in FOXF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-15). AlphaMissense: likely pathogenic (0.9993); Absent from gnomAD v4.1.

How common is FOXF1 p.Arg86Pro (c.257G>C) in the general population?

FOXF1 p.Arg86Pro (c.257G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FOXF1 p.Arg86Pro (c.257G>C)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

FOXF1 p.Arg86Pro

c.257G>C · rs2507450475 · VCV1710679

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic ✓ concordant with ClinVar · top 9% in FOXF1
REVEL	0.99	strongly pathogenic-leaning
SaProt	LLR -15.16	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 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.36	constrained · MANE · 125 bp · p 1.4e-06 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FOXF1
Protein: p.Arg86Pro
Coding: c.257G>C
MANE Select: NM_001451
dbSNP: rs2507450475
Type: single nucleotide variant
Location: chr16:86510826 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI 0.43 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 59.41
Residue 86: a DNA-binding region; a UniProt-annotated variant site (in acdmpv)

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

Similar variants

FOXF1 p.Arg86Trp Likely pathogenic ★ same residue
FOXF1 p.Arg86Gln Uncertain significance ⚠ same residue
FOXF1 p.Gln90Ter Pathogenic ★★ same type
FOXF1 p.Glu104Ter Pathogenic ★★ same type
FOXF1 p.Leu56Val Likely pathogenic ★★ same type
FOXF1 p.Ser223Ter Pathogenic ★★ same type
FOXF1 p.His357Leu Uncertain significance ★★ ⚠ same type
FOXF1 p.Met257Ile Uncertain significance ★★ ⚠ 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/foxf1-p-arg86pro (accessed [today's date]).

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