Is FOXH1 p.Pro12= (c.36A>C) pathogenic?

FOXH1 p.Pro12= (c.36A>C) is classified Likely benign in FOXH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). No allele count reported in gnomAD v4.1 (AN 1,413,622); Associated with holoprosencephaly.

What condition is associated with FOXH1 p.Pro12= (c.36A>C)?

FOXH1 p.Pro12= (c.36A>C) is associated with holoprosencephaly (ClinVar).

How common is FOXH1 p.Pro12= (c.36A>C) in the general population?

FOXH1 p.Pro12= (c.36A>C) is no allele count reported in gnomAD v4.1 (AN 1,413,622) (gnomAD).

FOXH1 p.Pro12=

c.36A>C · VCV4762717

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,413,622)

Conditions

holoprosencephaly

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 -5.1	GERP -3.6
Overall
CADD	0.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,413,622). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FOXH1
Protein: p.Pro12=
Coding: c.36A>C
MANE Select: NM_003923
Type: single nucleotide variant
Location: chr8:144475721 (GRCh38)
Gene constraint: LOEUF 1.608 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.00 · 2 PDB
Residue 12: the 'disordered' region

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

Disease context

holoprosencephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FOXH1 c.*74G>A Uncertain significance ★★ same condition
FOXH1 p.Ala136Ser Uncertain significance ★★ ⚠ same condition
FOXH1 p.Ala139Asp Uncertain significance ★★ ⚠ same condition
FOXH1 p.Ala249Val Uncertain significance ★★ ⚠ same condition
FOXH1 p.Ala271Val Uncertain significance ★★ ⚠ same condition
FOXH1 p.Ala43Val Uncertain significance ★★ ⚠ same condition
FOXH1 p.Arg129Gln Uncertain significance ★★ ⚠ same condition
FOXH1 p.Arg61Pro 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/foxh1-p-pro12 (accessed [today's date]).

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