AP1S1 p.Cys69=
c.207C>T · rs192601589 · VCV729962
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0219%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.046 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -7.5 | GERP -3.8 |
| Overall | ||
| CADD | 7.256 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0219%
European (non-Finnish) · 254/1,162,356 alleles
Filtering AF
0.0196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0187%
Overall
0.0177%
279/1,578,960 alleles · ultra-rare
exomes 263/1,426,652 · genomes 16/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0219% | 4,576 |
| Admixed American | 0.0182% | 5,485 |
| Remaining individualsnot grpmax-eligible | 0.0163% | 6,136 |
| African / African-American | 0.00405% | 24,721 |
| East Asian | 0.00233% | 42,942 |
| South Asian | 0.00116% | 85,846 |
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.Cys69=
- Coding
- c.207C>T
- MANE Select
- NM_001283
- dbSNP
- rs192601589
- Type
- single nucleotide variant
- Location
- chr7:101157401 (GRCh38)
- Gene constraint
- LOEUF 1.078 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.83 · 1 PDB
- Residue 69
- a β-strand
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-cys69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown