AP1S3 p.Glu89=
c.267G>A · rs998508971 · VCV3033468
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00333%, 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 3.3 | GERP 0.92, phastCons 1 |
| Overall | ||
| CADD | 10.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,008 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000248%
4/1,613,968 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,004 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| South Asian | 0.0011% | 91,070 |
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
- Protein
- p.Glu89=
- Coding
- c.267G>A
- MANE Select
- NM_001039569
- dbSNP
- rs998508971
- Type
- single nucleotide variant
- Location
- chr2:223775925 (GRCh38)
- Gene constraint
- LOEUF 0.817 · pLI 0.07 (gnomAD)
- Structure
- AlphaFold pLDDT 93.61 · 20 PDB
- Residue 89
- an α-helix
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-p-glu89 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown