Is FOXH1 p.Pro207= (c.621A>C) pathogenic?

FOXH1 p.Pro207= (c.621A>C) is classified Uncertain significance in FOXH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-19). Very rare (popmax 0.000263%, nfe).

How common is FOXH1 p.Pro207= (c.621A>C) in the general population?

FOXH1 p.Pro207= (c.621A>C) is very rare (popmax 0.000263%, nfe) (gnomAD).

FOXH1 p.Pro207=

c.621A>C · rs886044609 · VCV290986

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000263%, nfe)

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 -0.71	GERP -1.2, phastCons 0.008
Overall
CADD	1.119	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000263% European (non-Finnish) · 3/1,138,804 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000195% 3/1,534,594 alleles · very rare exomes 2/1,384,036 · genomes 1/150,558 · 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: FOXH1
Protein: p.Pro207=
Coding: c.621A>C
MANE Select: NM_003923
dbSNP: rs886044609
Type: single nucleotide variant
Location: chr8:144474715 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.00 · 2 PDB
Residue 207: the 'disordered' region

Full FOXH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FOXH1 p.Pro207Leu Uncertain significance ★ ⚠ same residue
FOXH1 p.Pro207Ser Uncertain significance ★ ⚠ same residue
FOXH1 c.*74G>A Uncertain significance ★★ same type
FOXH1 p.Ala136Ser Uncertain significance ★★ ⚠ same type
FOXH1 p.Ala139Asp Uncertain significance ★★ ⚠ same type
FOXH1 p.Ala249Val Uncertain significance ★★ ⚠ same type
FOXH1 p.Ala271Val Uncertain significance ★★ ⚠ same type
FOXH1 p.Ala43Val 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/foxh1-p-pro207 (accessed [today's date]).

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