APOA1 p.Phe253=
c.759C>T · VCV3616030
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
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 0.11 | GERP 2.2, phastCons 0.001 |
| Overall | ||
| CADD | 8.252 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,032 alleles
Overall
6.85e-05%
1/1,460,800 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
- APOA1
- Protein
- p.Phe253=
- Coding
- c.759C>T
- MANE Select
- NM_000039
- Type
- single nucleotide variant
- Location
- chr11:116835853 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.66 · 31 PDB
- Residue 253
- the '10 x approximate tandem repeats' region; a UniProt-annotated variant site (in fha2; no protein expression); a UniProt-annotated variant site (in hdl deficiency; with periorbital xanthelasmas; decreased protein abundance); a UniProt-annotated variant site (in fha2; missing protein expression); an α-helix
Similar variants
- APOA1 p.Phe253Cys Uncertain significance ★ 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-phe253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown