AP1S1 p.Thr23=
c.69T>G · rs775688954 · VCV2720494
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00502%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.083 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -3.8 |
| Overall | ||
| CADD | 1.64 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00502%
Admixed American · 3/59,726 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00067%
Overall
0.000682%
11/1,612,012 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00502% | 19,909 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,807 |
| European (non-Finnish) | 0.000424% | 235,847 |
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.Thr23=
- Coding
- c.69T>G
- MANE Select
- NM_001283
- dbSNP
- rs775688954
- Type
- single nucleotide variant
- Location
- chr7:101156659 (GRCh38)
- Gene constraint
- LOEUF 1.078 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.83 · 1 PDB
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-thr23 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown