ORC1 p.Lys152=
c.456G>A · rs146784241 · VCV698099
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.447%, afr)
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 -0.16 | GERP -1.8, phastCons 0.21 |
| Overall | ||
| CADD | 5.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.447%
African / African-American · 335/75,006 alleles
Filtering AF
0.407%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.392%
Overall
0.0238%
384/1,614,074 alleles · rare
exomes 192/1,461,870 · genomes 192/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.447% | 224 |
| Middle Eastern | 0.066% | 1,516 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| Admixed American | 0.0283% | 3,530 |
| European (non-Finnish) | 0.000508% | 196,667 |
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.Lys152=
- Coding
- c.456G>A
- MANE Select
- NM_004153
- dbSNP
- rs146784241
- Type
- single nucleotide variant
- Location
- chr1:52396311 (GRCh38)
- Gene constraint
- LOEUF 0.719 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.80 · 14 PDB
- Residue 152
- the bah domain
Similar variants
- 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
- ORC1 p.Ala597Thr 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-lys152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown