ORC4 p.Ser313=
c.939G>A · rs766925264 · VCV710596
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0055%, 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 -0.9 | GERP -3.7 |
| Overall | ||
| CADD | 7.361 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0055%
South Asian · 5/90,970 alleles
Filtering AF
0.00211%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00137%
Overall
0.00155%
25/1,607,978 alleles · very rare
exomes 21/1,455,850 · genomes 4/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0055% | 18,194 |
| Admixed American | 0.005% | 19,988 |
| East Asian | 0.00446% | 22,408 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,112 |
| African / African-American | 0.00267% | 37,387 |
| European (non-Finnish) | 0.000936% | 106,793 |
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.Ser313=
- Coding
- c.939G>A
- MANE Select
- NM_181741
- dbSNP
- rs766925264
- Type
- single nucleotide variant
- Location
- chr2:147939159 (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 313
- an α-helix
Similar variants
- ORC4 p.Ser313Trp Uncertain significance ★★ ⚠ same residue
- 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
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-ser313 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown