CYP27B1 p.Pro103=
c.309C>T · rs774932003 · VCV2167866
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0096%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.044 | GERP -3.8, phastCons 0.002 |
| Overall | ||
| CADD | 7.147 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0096%
Admixed American · 5/52,080 alleles
Filtering AF
0.00376%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00243%
Overall
0.000645%
10/1,551,396 alleles · very rare
exomes 6/1,399,146 · genomes 4/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0096% | 10,416 |
| Remaining individualsnot grpmax-eligible | 0.00166% | 60,368 |
| European (non-Finnish) | 0.000347% | 288,107 |
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
- CYP27B1
- Protein
- p.Pro103=
- Coding
- c.309C>T
- MANE Select
- NM_000785
- dbSNP
- rs774932003
- Type
- single nucleotide variant
- Location
- chr12:57766084 (GRCh38)
- Gene constraint
- LOEUF 1.1 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.75
Similar variants
- CYP27B1 c.196-2A>G Pathogenic/Likely pathogenic ★★ same type
- CYP27B1 c.590-1G>A Likely pathogenic ★★ same type
- CYP27B1 p.Ala129Val Likely pathogenic ★★ ⚠ same type
- CYP27B1 p.Arg389Cys Pathogenic ★★ same type
- CYP27B1 p.Arg389His Pathogenic/Likely pathogenic ★★ same type
- CYP27B1 p.Arg429Pro Pathogenic ★★ same type
- CYP27B1 p.Arg432Cys Pathogenic/Likely pathogenic ★★ same type
- CYP27B1 p.Arg453Cys Pathogenic/Likely pathogenic ★★ 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/cyp27b1-p-pro103 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown