ORC4 p.Val425=
c.1275G>A · rs1167416423 · VCV2978516
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, 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 |
|---|---|---|
| Pangolin | Δ0.50 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.48 | GERP -3.5, phastCons 0.85 |
| Overall | ||
| CADD | 5.262 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,002 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000186%
3/1,613,850 alleles · very rare
exomes 3/1,461,560 · genomes 0/152,290 · 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
- ORC4
- Protein
- p.Val425=
- Coding
- c.1275G>A
- MANE Select
- NM_181741
- dbSNP
- rs1167416423
- Type
- single nucleotide variant
- Location
- chr2:147935546 (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 425
- 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-val425 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown