AP2S1 p.Ile5=
c.15C>T · rs201984742 · VCV1133465
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -0.6, phastCons 1 |
| Overall | ||
| CADD | 15.65 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,884 alleles
Filtering AF
0.00215%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00191%
Overall
0.00248%
40/1,613,998 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,442 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| European (non-Finnish) | 0.00297% | 33,714 |
| Finnishnot grpmax-eligible | 0.00156% | 64,030 |
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
- AP2S1
- Protein
- p.Ile5=
- Coding
- c.15C>T
- MANE Select
- NM_004069
- dbSNP
- rs201984742
- Type
- single nucleotide variant
- Location
- chr19:46846131 (GRCh38)
- Gene constraint
- LOEUF 0.478 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 97.03 · 1 PDB
- Residue 5
- a β-strand
Similar variants
- AP2S1 p.Ile5Val Uncertain significance ★ ⚠ same residue
- AP2S1 p.Arg15Cys Pathogenic ★★ same type
- AP2S1 p.Arg15His Pathogenic/Likely pathogenic ★★ same type
- AP2S1 p.Arg15Leu Pathogenic ★★ same type
- AP2S1 c.153+5C>T Uncertain significance ★★ same type
- AP2S1 p.Arg60His Uncertain significance ★★ ⚠ same type
- AP2S1 p.Gln22His Uncertain significance ★★ ⚠ same type
- AP2S1 p.Ile84Val 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/ap2s1-p-ile5 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown