APOB p.Asn1256=
c.3768T>C · rs1341925701 · VCV794844
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00127%, nfe)
Conditions
2
familial hypobetalipoproteinemia 1
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 -0.69 | GERP -3.4 |
| Overall | ||
| CADD | 0.717 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00127%
European (non-Finnish) · 15/1,179,990 alleles
Filtering AF
0.000763%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000605%
Overall
0.00103%
15/1,461,836 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.Asn1256=
- Coding
- c.3768T>C
- MANE Select
- NM_000384
- dbSNP
- rs1341925701
- Type
- single nucleotide variant
- Location
- chr2:21014522 (GRCh38)
- Gene constraint
- LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Similar variants
- APOB p.Asn1256Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-asn1256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown