ORC1 p.Ala480=
c.1440T>C · rs543395954 · VCV1672941
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.107%, eas)
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 -0.89 | GERP -4.4 |
| Overall | ||
| CADD | 3.366 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.107%
East Asian · 48/44,884 alleles
Filtering AF
0.0829%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0743%
Overall
0.0031%
50/1,613,916 alleles · rare
exomes 43/1,461,556 · genomes 7/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.107% | 935 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
| European (non-Finnish) | 8.47e-05% | 1,180,006 |
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.Ala480=
- Coding
- c.1440T>C
- MANE Select
- NM_004153
- dbSNP
- rs543395954
- Type
- single nucleotide variant
- Location
- chr1:52385893 (GRCh38)
- Gene constraint
- LOEUF 0.719 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.80 · 14 PDB
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-ala480 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown