APOB p.Leu4189=
c.12567G>A · rs781627851 · VCV2145418
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, amr)
Conditions
3
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 -2.2 | GERP -1.3 |
| Overall | ||
| CADD | 1.033 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
Admixed American · 16/59,918 alleles
Filtering AF
0.0167%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.000992%
16/1,613,394 alleles · ultra-rare
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
- APOB
- Protein
- p.Leu4189=
- Coding
- c.12567G>A
- MANE Select
- NM_000384
- dbSNP
- rs781627851
- Type
- single nucleotide variant
- Location
- chr2:21002855 (GRCh38)
- Gene constraint
- LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Similar variants
- APOB c.1830-1G>A Pathogenic ★★ same condition
- APOB c.2604+1G>A Likely pathogenic ★★ same condition
- APOB c.537+1G>T Pathogenic/Likely pathogenic ★★ same condition
- APOB p.Arg1333Ter Pathogenic ★★ same condition
- APOB p.Arg2012Ter Pathogenic ★★ same condition
- APOB p.Arg2085Ter Pathogenic/Likely pathogenic ★★ same condition
- APOB p.Arg2513Ter Pathogenic ★★ same condition
- APOB p.Arg2520Ter Pathogenic/Likely pathogenic ★★ 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/apob-p-leu4189 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown