ORC1 p.Pro812=
c.2436G>A · rs776580786 · VCV436114
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.118%, amr)
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 -20 | GERP -4.7 |
| Overall | ||
| CADD | 0.071 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.118%
Admixed American · 71/59,994 alleles
Filtering AF
0.0962%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0881%
Overall
0.0052%
84/1,613,968 alleles · rare
exomes 75/1,461,828 · genomes 9/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.118% | 845 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,830 |
| African / African-American | 0.00267% | 37,440 |
| European (non-Finnish) | 0.000678% | 147,500 |
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.Pro812=
- Coding
- c.2436G>A
- MANE Select
- NM_004153
- dbSNP
- rs776580786
- Type
- single nucleotide variant
- Location
- chr1:52373331 (GRCh38)
- Gene constraint
- LOEUF 0.719 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.80 · 14 PDB
- Residue 812
- the 'necessary and sufficient for orc complex assembly' region; an α-helix
Similar variants
- ORC1 p.Pro812Leu Uncertain significance ★★ ⚠ same residue
- ORC1 c.721+1G>C Likely pathogenic ★★ same type
- ORC1 p.Arg105Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- ORC1 p.Arg105Trp Likely pathogenic ★★ ⚠ same type
- ORC1 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same type
- ORC1 p.Arg720Gln Likely pathogenic ★★ same type
- ORC1 p.Ala174Val Uncertain significance ★★ ⚠ same type
- ORC1 p.Ala205Gly Uncertain significance ★★ ⚠ 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/orc1-p-pro812 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown