ORC4 p.Leu76=
c.228A>G · VCV4763722
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Not reported
no allele count reported in gnomAD v4.1 (AN 1,194,558)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 0.58, phastCons 1 |
| Overall | ||
| CADD | 15.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
No allele count reported in gnomAD v4.1 (AN 1,194,558). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- ORC4
- Protein
- p.Leu76=
- Coding
- c.228A>G
- MANE Select
- NM_181741
- Type
- single nucleotide variant
- Location
- chr2:147958864 (GRCh38)
- Gene constraint
- LOEUF 1.532 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.12 · 15 PDB
- Residue 76
- an α-helix
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-leu76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown