AP1S1 p.Arg33=
c.99C>T · rs77387752 · VCV785736
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.72%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.079 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.38 | donor gain · deltas |
| Constraint at this position | ||
| Conservation | phyloP -0.74 | GERP -3.8 |
| Overall | ||
| CADD | 16.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.72%
East Asian · 2,113/44,744 alleles
Filtering AF
4.55%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.49%
Overall
0.524%
8,430/1,609,950 alleles · low-frequency
exomes 7,596/1,457,708 · genomes 834/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 4.72% | 21 |
| South Asian | 1.02% | 99 |
| Remaining individualsnot grpmax-eligible | 0.912% | 110 |
| Admixed American | 0.493% | 203 |
| European (non-Finnish) | 0.373% | 268 |
| African / African-American | 0.152% | 657 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0815% | 1,226 |
| Middle Eastern | 0.0661% | 1,514 |
| Finnishnot grpmax-eligible | 0.011% | 9,112 |
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
- AP1S1
- Protein
- p.Arg33=
- Coding
- c.99C>T
- MANE Select
- NM_001283
- dbSNP
- rs77387752
- Type
- single nucleotide variant
- Location
- chr7:101156689 (GRCh38)
- Gene constraint
- LOEUF 1.078 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.83 · 1 PDB
- Residue 33
- an α-helix
Similar variants
- AP1S1 c.183-1G>C Pathogenic/Likely pathogenic ★★ same type
- AP1S1 c.183-2A>G Pathogenic ★★ same type
- AP1S1 c.291+2T>A Pathogenic/Likely pathogenic ★★ same type
- AP1S1 p.Gln74Ter Pathogenic/Likely pathogenic ★★ same type
- AP1S1 p.Tyr62Ter Pathogenic/Likely pathogenic ★★ same type
- AP1S1 c.182+252C>T Benign ★★ same type
- AP1S1 c.182+78T>C Benign ★★ same type
- AP1S1 c.183-17T>C Likely 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/ap1s1-p-arg33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown