APOA1 p.Ser60=
c.180C>T · VCV4755206
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
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 -1.4 | GERP -0.84 |
| Overall | ||
| CADD | 6.655 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,894 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.00185%
27/1,461,808 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,413 |
| Finnishnot grpmax-eligible | 0.00469% | 21,319 |
| South Asian | 0.00439% | 22,772 |
| Admixed American | 0.00167% | 60,034 |
| European (non-Finnish) | 0.00102% | 98,337 |
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
- APOA1
- Protein
- p.Ser60=
- Coding
- c.180C>T
- MANE Select
- NM_000039
- Type
- single nucleotide variant
- Location
- chr11:116837021 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.66 · 31 PDB
- Residue 60
- a UniProt-annotated variant site (in fha2; no protein expression); a UniProt-annotated variant site (in hdl deficiency; with periorbital xanthelasmas; decreased protein abundance)
Similar variants
- APOA1 p.Ser60Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
- APOA1 p.Arg197Pro Pathogenic ★★ same type
- APOA1 p.Gln23Ter Pathogenic ★★ same type
- APOA1 p.Gly50Arg Pathogenic ★★ same type
- APOA1 c.-21+22G>A Uncertain significance ★★ same type
- APOA1 p.Ala176Thr Uncertain significance ★★ ⚠ same type
- APOA1 p.Ala176Val Uncertain significance ★★ ⚠ same type
- APOA1 p.Ala204Val Uncertain significance ★★ ⚠ same type
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/apoa1-p-ser60 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown