AKAP8 p.Ser501=
c.1503C>T · rs199943338 · VCV2649492
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, amr)
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 -4.7 | GERP -4.8 |
| Overall | ||
| CADD | 2.655 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
Admixed American · 16/59,940 alleles
Filtering AF
0.0167%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00298%
48/1,613,422 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0267% | 3,746 |
| Middle Eastern | 0.0167% | 5,978 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,942 |
| European (non-Finnish) | 0.0017% | 58,989 |
| African / African-American | 0.00133% | 75,042 |
| South Asian | 0.0011% | 90,930 |
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
- AKAP8
- Protein
- p.Ser501=
- Coding
- c.1503C>T
- MANE Select
- NM_005858
- dbSNP
- rs199943338
- Type
- single nucleotide variant
- Location
- chr19:15360872 (GRCh38)
- Gene constraint
- LOEUF 0.48 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 53.67
Similar variants
- AKAP8 p.Ala40Thr Uncertain significance ★★ ⚠ same type
- AKAP8 c.1072+7A>C Benign ★★ same type
- AKAP8 p.Ala615= Benign ★★ same type
- AKAP8 p.Arg206His Benign ★★ same type
- AKAP8 p.Arg320Gln Likely benign ★★ ⚠ same type
- AKAP8 p.Asp687= Likely benign ★★ same type
- AKAP8 p.Glu226Lys Likely benign ★★ same type
- AKAP8 p.Gly167Glu 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/akap8-p-ser501 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown