AKAP1 p.Leu548=
c.1644G>A · rs11658676 · VCV727132
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.117%, 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 5.1 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 12.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.117%
European (non-Finnish) · 1,386/1,180,030 alleles
Filtering AF
0.112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.11%
Overall
0.0974%
1,573/1,614,212 alleles · rare
exomes 1,490/1,461,868 · genomes 83/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.117% | 851 |
| South Asian | 0.113% | 884 |
| Middle Eastern | 0.099% | 1,010 |
| Remaining individualsnot grpmax-eligible | 0.08% | 1,250 |
| African / African-American | 0.016% | 6,255 |
| Admixed American | 0.015% | 6,670 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0135% | 7,401 |
| Finnishnot grpmax-eligible | 0.00468% | 21,347 |
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.Leu548=
- Coding
- c.1644G>A
- MANE Select
- NM_003488
- dbSNP
- rs11658676
- Type
- single nucleotide variant
- Location
- chr17:57107108 (GRCh38)
- Gene constraint
- LOEUF 0.526 · pLI 0.67 (gnomAD)
- Structure
- AlphaFold pLDDT 57.02
Similar variants
- 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.Pro818= 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-leu548 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown