AP1S3 c.3+9G>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.121%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +9 | near-intronic (+9 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -1.5 |
| Non-coding constraint | Z 3.44 | 1 kb window · o/e 0.75 · regional · uncalibrated |
| Overall | ||
| CADD | 2.852 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.121%
East Asian · 39/32,164 alleles
Filtering AF
0.0911%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0807%
Overall
0.0041%
52/1,267,012 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.121% | 825 |
| Middle Eastern | 0.0297% | 3,364 |
| South Asian | 0.00285% | 35,028 |
| Remaining individualsnot grpmax-eligible | 0.00213% | 46,998 |
| European (non-Finnish) | 0.000997% | 100,282 |
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
- AP1S3
- Coding
- c.3+9G>C
- MANE Select
- NM_001039569
- dbSNP
- rs747747935
- Type
- single nucleotide variant
- Location
- chr2:223837439 (GRCh38)
- Gene constraint
- LOEUF 0.817 · pLI 0.07 (gnomAD)
- Structure
- AlphaFold pLDDT 93.61 · 20 PDB
Similar variants
- AP1S3 p.Arg86Cys Uncertain significance ★★ ⚠ same type
- AP1S3 p.Arg33Trp Benign/Likely benign ★★ same type
- AP1S3 p.Ile83Thr Benign/Likely benign ★★ ⚠ same type
- AP1S3 p.Phe4Cys Benign/Likely benign ★★ same type
- AP1S3 p.Thr22Ala Likely benign ★★ same type
- AP1S3 p.Arg10Ter Uncertain significance ★ same type
- AP1S3 p.Arg42Ser Uncertain significance ★ ⚠ same type
- AP1S3 p.Asp115His 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/ap1s3-c-3-plus-9g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown