ORC1 p.Ser269=
c.807G>A · rs769149749 · VCV1105173
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.011%, sas)
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 0.58 | GERP -4.4, phastCons 0.94 |
| Overall | ||
| CADD | 6.446 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.011%
South Asian · 10/91,034 alleles
Filtering AF
0.00594%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00453%
Overall
0.00186%
30/1,613,944 alleles · ultra-rare
exomes 29/1,461,744 · genomes 1/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.011% | 9,103 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,251 |
| Admixed American | 0.00167% | 59,982 |
| European (non-Finnish) | 0.00144% | 69,411 |
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.Ser269=
- Coding
- c.807G>A
- MANE Select
- NM_004153
- dbSNP
- rs769149749
- Type
- single nucleotide variant
- Location
- chr1:52393718 (GRCh38)
- Gene constraint
- LOEUF 0.719 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.80 · 14 PDB
- Residue 269
- the 'disordered' region
Similar variants
- ORC1 p.Ser269Leu Benign/Likely benign ★★ 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-ser269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown