APOL1 p.Ala218=
c.654C>A · rs136174 · VCV1170848
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 94.7%, 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 -20 | GERP -3.8 |
| Overall | ||
| CADD | 0.209 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
94.7%
African / African-American · 70,987/74,992 alleles
Filtering AF
94.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 93.8%
Overall
82.1%
1,324,661/1,613,798 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 94.7% | 1 |
| Admixed American | 89.5% | 1 |
| Finnishnot grpmax-eligible | 84.2% | 1 |
| East Asian | 83.3% | 1 |
| South Asian | 82.9% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 82% | 1 |
| Remaining individualsnot grpmax-eligible | 81.9% | 1 |
| European (non-Finnish) | 80.7% | 1 |
| Amishnot grpmax-eligible | 76.4% | 1 |
| Middle Eastern | 76.2% | 1 |
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
- APOL1
- Protein
- p.Ala218=
- Coding
- c.654C>A
- MANE Select
- NM_003661
- dbSNP
- rs136174
- Type
- single nucleotide variant
- Location
- chr22:36265490 (GRCh38)
- Gene constraint
- LOEUF 1.68 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.94 · 5 PDB
- Residue 218
- the 'pore-forming region' region
Similar variants
- APOL1 p.Ala108Glu Uncertain significance ★★ ⚠ same type
- APOL1 p.Ala394Gly Uncertain significance ★★ ⚠ same type
- APOL1 p.Arg112Cys Uncertain significance ★★ ⚠ same type
- APOL1 p.Asp46Gly Uncertain significance ★★ ⚠ same type
- APOL1 p.Gln396Ter Uncertain significance ★★ same type
- APOL1 p.Glu110Asp Uncertain significance ★★ ⚠ same type
- APOL1 p.Glu323Gln Uncertain significance ★★ ⚠ same type
- APOL1 p.His298Arg 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/apol1-p-ala218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown