ORC1 p.Pro63=
c.189G>T · rs201244952 · VCV874949
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.187%, eas)
Conditions
1
Meier-Gorlin syndrome 1
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 -8.6 | GERP -4.3 |
| Overall | ||
| CADD | 0.046 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.187%
East Asian · 84/44,874 alleles
Filtering AF
0.155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.143%
Overall
0.00539%
87/1,613,984 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.187% | 534 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
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
- ORC1
- Protein
- p.Pro63=
- Coding
- c.189G>T
- MANE Select
- NM_014252 · reported on NM_004153
- dbSNP
- rs201244952
- Type
- single nucleotide variant
- Location
- chr1:52401396 (GRCh38)
- Structure
- AlphaFold pLDDT 87.43
Similar variants
- ORC1 p.Arg105Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ORC1 p.Arg105Trp Likely pathogenic ★★ ⚠ same condition
- ORC1 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same condition
- ORC1 p.Arg720Gln Likely pathogenic ★★ same condition
- ORC1 p.Ala174Val Uncertain significance ★★ ⚠ same condition
- ORC1 p.Ala597Thr Uncertain significance ★★ ⚠ same condition
- ORC1 p.Ala857Val Uncertain significance ★★ ⚠ same condition
- ORC1 p.Ala97Ser 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/orc1-p-pro63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown