CRTAP p.Pro289=
c.867G>A · rs746374230 · VCV1086452
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
osteogenesis imperfecta type 7
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 -12 | GERP -4.5 |
| Overall | ||
| CADD | 0.384 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,018 alleles
Filtering AF
0.0005%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000806%
13/1,613,612 alleles · very rare
exomes 13/1,461,352 · genomes 0/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,018 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| European (non-Finnish) | 0.000933% | 107,234 |
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
- CRTAP
- Protein
- p.Pro289=
- Coding
- c.867G>A
- MANE Select
- NM_006371
- dbSNP
- rs746374230
- Type
- single nucleotide variant
- Location
- chr3:33130012 (GRCh38)
- Gene constraint
- LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.81 · 6 PDB
Similar variants
- CRTAP p.Pro289Leu Uncertain significance ★★ ⚠ same residue
- CRTAP c.471+2C>A Pathogenic/Likely pathogenic ★★ same condition
- CRTAP p.Arg212Ter Pathogenic/Likely pathogenic ★★ same condition
- CRTAP p.Gln276Ter Pathogenic ★★ same condition
- CRTAP p.Tyr148Ter Pathogenic/Likely pathogenic ★★ same condition
- CRTAP p.Tyr340Ter Pathogenic/Likely pathogenic ★★ same condition
- CRTAP p.Tyr66Ter Pathogenic ★★ same condition
- CRTAP c.*3221C>T 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/crtap-p-pro289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown