APOA4 p.Ala333=
c.999G>A · VCV3714191
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00833%, 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 -1.4 | GERP 1.6 |
| Overall | ||
| CADD | 6.066 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,018 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00206%
Overall
0.000991%
16/1,614,094 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00833% | 12,004 |
| African / African-American | 0.00534% | 18,732 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| Finnishnot grpmax-eligible | 0.00156% | 64,010 |
| South Asian | 0.0011% | 91,088 |
| European (non-Finnish) | 0.000339% | 295,016 |
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.Ala333=
- Coding
- c.999G>A
- MANE Select
- NM_000482
- Type
- single nucleotide variant
- Location
- chr11:116821059 (GRCh38)
- Gene constraint
- LOEUF 0.985 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.14 · 2 PDB
Similar variants
- APOA4 p.Ala333Val Uncertain significance ★★ ⚠ same residue
- APOA4 p.Ala333Gly Uncertain significance ★ ⚠ same residue
- APOA4 p.Ala172Thr 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-ala333 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown