AP1S1 p.Gln142=
c.426A>G · rs200415338 · VCV2735533
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0084%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.11 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.9 | GERP -0.25, phastCons 1 |
| Overall | ||
| CADD | 8.811 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0084%
European (non-Finnish) · 99/1,178,510 alleles
Filtering AF
0.00703%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00652%
Overall
0.00633%
102/1,610,536 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0084% | 11,904 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,199 |
| South Asian | 0.00111% | 90,468 |
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.Gln142=
- Coding
- c.426A>G
- MANE Select
- NM_001283
- dbSNP
- rs200415338
- Type
- single nucleotide variant
- Location
- chr7:101159193 (GRCh38)
- Gene constraint
- LOEUF 1.078 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.83 · 1 PDB
- Residue 142
- 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-gln142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown