ORC1 p.Ser217=
c.651C>T · VCV3614682
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, 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 -4 | GERP -4.6 |
| Overall | ||
| CADD | 0.173 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,094 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000743%
12/1,614,036 alleles · very rare
exomes 10/1,461,892 · genomes 2/152,144 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,547 |
| Admixed American | 0.00167% | 59,992 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| African / African-American | 0.00134% | 74,900 |
| European (non-Finnish) | 0.000593% | 168,577 |
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.Ser217=
- Coding
- c.651C>T
- MANE Select
- NM_004153
- Type
- single nucleotide variant
- Location
- chr1:52396116 (GRCh38)
- Gene constraint
- LOEUF 0.719 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.80 · 14 PDB
- Residue 217
- the 'disordered' region
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-ser217 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown