APOC3 p.Arg4=
c.12G>A · rs745897503 · VCV2565487
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Conditions
1
Cardiovascular phenotype
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 1.8 | GERP 2.5, phastCons 0.96 |
| Overall | ||
| CADD | 10.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.00594%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00453%
Overall
0.00171%
25/1,461,736 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| South Asian | 0.011% | 9,109 |
| European (non-Finnish) | 0.0011% | 90,770 |
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
- APOC3
- Protein
- p.Arg4=
- Coding
- c.12G>A
- MANE Select
- NM_000040
- dbSNP
- rs745897503
- Type
- single nucleotide variant
- Location
- chr11:116830594 (GRCh38)
- Gene constraint
- LOEUF 1.68 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.90 · 1 PDB
Similar variants
- APOC3 p.Arg4Trp Uncertain significance ★ ⚠ same residue
- APOC3 p.Glu24Lys Uncertain significance ★★ ⚠ same condition
- APOC3 p.Leu14Phe Uncertain significance ★★ ⚠ same condition
- APOC3 p.Val91Ile Uncertain significance ★★ ⚠ same condition
- APOC3 p.Ala16= Likely benign ★★ same condition
- APOC3 p.Ala23= Benign/Likely benign ★★ same condition
- APOC3 p.Gln33= Benign/Likely benign ★★ same condition
- APOC3 p.Gly34= Benign ★★ same condition
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/apoc3-p-arg4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown