Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 65.6%, afr) — too common for a highly-penetrant pathogenic allele
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 0.001 | GERP -3.7, phastCons 0.76 |
| Overall | ||
| CADD | 8.809 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
65.6%
African / African-American · 31,885/48,636 alleles
Filtering AF
65%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 64.7%
Overall
57.4%
228,700/398,648 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 65.6% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 62.3% | 2 |
| South Asian | 61.9% | 2 |
| European (non-Finnish) | 57.9% | 2 |
| Remaining individualsnot grpmax-eligible | 56.9% | 2 |
| Middle Eastern | 55.7% | 2 |
| Amishnot grpmax-eligible | 55% | 2 |
| Admixed American | 51% | 2 |
| East Asian | 50.2% | 2 |
| Finnishnot grpmax-eligible | 49.2% | 2 |
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
- APELA
- Protein
- p.Phe53=
- Coding
- c.159T>C
- MANE Select
- NM_001297550
- dbSNP
- rs4541465
- Type
- single nucleotide variant
- Location
- chr4:164879002 (GRCh38)
- Structure
- AlphaFold pLDDT 72.73 · 3 PDB
Similar variants
- APELA p.Phe8= Likely benign ★★ 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/apela-p-phe53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown