ORC6 p.Glu4=
c.12G>A · rs566287766 · VCV2963034
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0239%, 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 -0.9 | GERP -2.8 |
| Overall | ||
| CADD | 5.692 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0239%
Admixed American · 14/58,646 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0115%
Overall
0.002%
32/1,601,896 alleles · ultra-rare
exomes 28/1,449,572 · genomes 4/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0239% | 4,189 |
| European (non-Finnish) | 0.00153% | 65,246 |
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
- ORC6
- Protein
- p.Glu4=
- Coding
- c.12G>A
- MANE Select
- NM_014321
- dbSNP
- rs566287766
- Type
- single nucleotide variant
- Location
- chr16:46689717 (GRCh38)
- Gene constraint
- LOEUF 1.784 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 81.69 · 4 PDB
- Residue 4
- an α-helix
Similar variants
- ORC6 p.Ala10Ser Uncertain significance ★★ ⚠ same type
- ORC6 p.Arg8His Uncertain significance ★★ ⚠ same type
- ORC6 p.Arg8Leu Uncertain significance ★★ ⚠ same type
- ORC6 p.Gln130His Uncertain significance ★★ ⚠ same type
- ORC6 p.Ile69Met Uncertain significance ★★ ⚠ same type
- ORC6 p.Leu228Val Uncertain significance ★★ ⚠ same type
- ORC6 p.Leu92Pro Uncertain significance ★★ ⚠ same type
- ORC6 p.Met218Arg 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/orc6-p-glu4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown