APOA4 p.Ala5=
c.15C>T · rs370537175 · VCV3050176
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0467%, amr)
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 -2.5 | GERP -7.5 |
| Overall | ||
| CADD | 1.571 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0467%
Admixed American · 28/60,000 alleles
Filtering AF
0.0331%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0286%
Overall
0.00719%
116/1,613,948 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0467% | 2,143 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,248 |
| European (non-Finnish) | 0.00627% | 15,946 |
| South Asian | 0.00329% | 30,364 |
| African / African-American | 0.00133% | 74,916 |
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
- APOA4
- Protein
- p.Ala5=
- Coding
- c.15C>T
- MANE Select
- NM_000482
- dbSNP
- rs370537175
- Type
- single nucleotide variant
- Location
- chr11:116823177 (GRCh38)
- Gene constraint
- LOEUF 0.985 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.14 · 2 PDB
Similar variants
- APOA4 p.Ala5Thr Uncertain significance ★ ⚠ same residue
- APOA4 p.Ala172Thr Uncertain significance ★★ ⚠ same type
- APOA4 p.Ala333Val Uncertain significance ★★ ⚠ same type
- APOA4 p.Ala60Asp Uncertain significance ★★ ⚠ same type
- APOA4 p.Arg166Ser Uncertain significance ★★ ⚠ same type
- APOA4 p.Arg275Cys Uncertain significance ★★ ⚠ same type
- APOA4 p.Gln50Arg Uncertain significance ★★ ⚠ same type
- APOA4 p.Gln50Lys 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/apoa4-p-ala5 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown