APOB p.Asp1997=
c.5991T>C · VCV4888250
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
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 0.23 | GERP -3.8, phastCons 0.006 |
| Overall | ||
| CADD | 3.175 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,084 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000372%
6/1,614,020 alleles · very rare
exomes 5/1,461,858 · genomes 1/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,217 |
| European (non-Finnish) | 8.47e-05% | 1,180,027 |
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.Asp1997=
- Coding
- c.5991T>C
- MANE Select
- NM_000384
- Type
- single nucleotide variant
- Location
- chr2:21010877 (GRCh38)
- Gene constraint
- LOEUF 0.537 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Similar variants
- APOB p.Asp1997Asn Likely benign ★★ same residue
- APOB p.Asp1997Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
- APOB p.Asp1997Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-asp1997 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown