ORC4 p.Leu321=
c.963A>G · rs78758762 · VCV729067
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.917%, 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 -6.5 | GERP -4 |
| Overall | ||
| CADD | 0.312 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.917%
African / African-American · 678/73,972 alleles
Filtering AF
0.859%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.837%
Overall
0.0491%
770/1,568,650 alleles · rare
exomes 351/1,416,466 · genomes 419/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.917% | 109 |
| Admixed American | 0.0634% | 1,577 |
| Remaining individualsnot grpmax-eligible | 0.0493% | 2,030 |
| South Asian | 0.00887% | 11,269 |
| European (non-Finnish) | 0.0014% | 71,288 |
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
- ORC4
- Protein
- p.Leu321=
- Coding
- c.963A>G
- MANE Select
- NM_181741
- dbSNP
- rs78758762
- Type
- single nucleotide variant
- Location
- chr2:147938389 (GRCh38)
- Gene constraint
- LOEUF 1.532 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.12 · 15 PDB
Similar variants
- ORC4 p.Ser208Ter Pathogenic/Likely pathogenic ★★ same type
- ORC4 p.Tyr174Cys Pathogenic/Likely pathogenic ★★ same type
- ORC4 p.Ala375Pro Uncertain significance ★★ ⚠ same type
- ORC4 p.Arg116Lys Uncertain significance ★★ ⚠ same type
- ORC4 p.Arg148Gln Uncertain significance ★★ ⚠ same type
- ORC4 p.Arg213Gln Uncertain significance ★★ same type
- ORC4 p.Arg25His Uncertain significance ★★ same type
- ORC4 p.Asn106Ser 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/orc4-p-leu321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown