ORC6 p.Pro219=
c.657A>G · rs146875138 · VCV1899849
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00136%, nfe)
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 4.9 |
| Overall | ||
| CADD | 8.332 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00136%
European (non-Finnish) · 16/1,179,454 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.000992%
16/1,613,550 alleles · very rare
exomes 16/1,461,218 · genomes 0/152,332 · joint denominator
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.Pro219=
- Coding
- c.657A>G
- MANE Select
- NM_014321
- dbSNP
- rs146875138
- Type
- single nucleotide variant
- Location
- chr16:46697483 (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 219
- the 'disordered' region; 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-pro219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown