AKAP4 p.Ser447=
c.1341A>G · rs782817329 · VCV2660539
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0229%, mid)
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 -1.7 | GERP -3.4 |
| Overall | ||
| CADD | 0.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0229%
Middle Eastern · 1/4,375 alleles
Filtering AF
0.000725%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000482%
Overall
0.00116%
14/1,209,802 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0229% | 4,375 |
| Admixed American | 0.00437% | 22,873 |
| European (non-Finnish) | 0.00123% | 81,378 |
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
- AKAP4
- Protein
- p.Ser447=
- Coding
- c.1341A>G
- MANE Select
- NM_003886
- dbSNP
- rs782817329
- Type
- single nucleotide variant
- Location
- chrX:50193372 (GRCh38)
- Structure
- AlphaFold pLDDT 53.52
- Residue 447
- a modified residue (phosphoserine)
Similar variants
- AKAP4 p.Arg429His Uncertain significance ★★ ⚠ same type
- AKAP4 p.Ala150Gly Uncertain significance ★ ⚠ same type
- AKAP4 p.Ala449Val Uncertain significance ★ ⚠ same type
- AKAP4 p.Ala593Val Uncertain significance ★ ⚠ same type
- AKAP4 p.Ala719Glu Uncertain significance ★ ⚠ same type
- AKAP4 p.Ala731Pro Uncertain significance ★ ⚠ same type
- AKAP4 p.Ala809Val Uncertain significance ★ ⚠ same type
- AKAP4 p.Arg294Ser 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/akap4-p-ser447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown