AKAP1 p.Pro818=
c.2454G>A · rs116339701 · VCV786656
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.39%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8 | GERP -3.2 |
| Overall | ||
| CADD | 0.225 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.39%
African / African-American · 2,544/75,042 alleles
Filtering AF
3.28%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.24%
Overall
0.188%
3,038/1,614,186 alleles · low-frequency
exomes 1,579/1,461,874 · genomes 1,459/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.39% | 29 |
| Admixed American | 0.298% | 335 |
| Remaining individualsnot grpmax-eligible | 0.246% | 406 |
| Middle Eastern | 0.115% | 866 |
| European (non-Finnish) | 0.012% | 8,310 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00675% | 14,804 |
| East Asian | 0.00668% | 14,961 |
| South Asian | 0.00659% | 15,181 |
| Finnishnot grpmax-eligible | 0.00156% | 64,036 |
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
- AKAP1
- Protein
- p.Pro818=
- Coding
- c.2454G>A
- MANE Select
- NM_003488
- dbSNP
- rs116339701
- Type
- single nucleotide variant
- Location
- chr17:57116881 (GRCh38)
- Gene constraint
- LOEUF 0.526 · pLI 0.67 (gnomAD)
- Structure
- AlphaFold pLDDT 57.02
Similar variants
- AKAP1 p.Pro818Leu Uncertain significance ★ ⚠ same residue
- AKAP1 c.1976-6A>G Benign ★★ same type
- AKAP1 p.Ala218Thr Benign ★★ same type
- AKAP1 p.Gly323Ser Benign ★★ same type
- AKAP1 p.Pro475= Benign ★★ same type
- AKAP1 p.Ser330Gly Benign ★★ same type
- AKAP1 p.Ser388= Benign ★★ same type
- AKAP1 p.Thr521Ile 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/akap1-p-pro818 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown