GCH1 p.Pro9=
c.27G>C · rs1361472755 · VCV1552714
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000892%, nfe)
Conditions
2
GTP cyclohydrolase I deficiency
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 0.12 | GERP -0.36 |
| Overall | ||
| CADD | 6.063 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000892%
European (non-Finnish) · 10/1,121,562 alleles
Filtering AF
0.000451%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000329%
Overall
0.000674%
10/1,484,024 alleles · very rare
exomes 10/1,331,810 · genomes 0/152,214 · 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
- GCH1
- Protein
- p.Pro9=
- Coding
- c.27G>C
- MANE Select
- NM_000161
- dbSNP
- rs1361472755
- Type
- single nucleotide variant
- Location
- chr14:54902637 (GRCh38)
- Gene constraint
- LOEUF 0.899 · pLI 0.36 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 86.89 · 11 PDB
- Residue 9
- the 'disordered' region
Similar variants
- GCH1 p.Pro9Ser Uncertain significance ★ ⚠ same residue
- GCH1 c.344-1G>A Pathogenic ★★ same condition
- GCH1 c.510-1G>A Pathogenic/Likely pathogenic ★★ same condition
- GCH1 c.541+1G>T Pathogenic ★★ same condition
- GCH1 c.541+2T>C Pathogenic ★★ same condition
- GCH1 c.626+1G>A Pathogenic/Likely pathogenic ★★ same condition
- GCH1 c.626+1G>T Pathogenic ★★ same condition
- GCH1 c.-22C>T Pathogenic/Likely pathogenic ★★ 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/gch1-p-pro9 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown