APOB p.Arg4106=
c.12316A>C · VCV3571445
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.54e-05%, nfe)
Conditions
1
familial hypercholesterolemia
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 0.66 | GERP -2.1 |
| Overall | ||
| CADD | 3.853 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.54e-05%
European (non-Finnish) · 1/1,171,342 alleles
Overall
6.91e-05%
1/1,446,686 alleles · very 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.Arg4106=
- Coding
- c.12316A>C
- MANE Select
- NM_000384
- Type
- single nucleotide variant
- Location
- chr2:21003106 (GRCh38)
- Gene constraint
- LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Similar variants
- APOB p.Arg2085Ter Pathogenic/Likely pathogenic ★★ same condition
- APOB p.Arg3527Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
- APOB p.Arg3527Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- APOB p.Ala1695Val Uncertain significance ★★ ⚠ same condition
- APOB p.Ala68Thr Uncertain significance ★★ ⚠ same condition
- APOB p.Arg3183Gly Uncertain significance ★★ ⚠ same condition
- APOB p.Arg3311Ile Uncertain significance ★★ ⚠ same condition
- APOB p.Asn3358His Uncertain significance ★★ 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-arg4106 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown