AP1S1 p.Ser147=
c.441G>A · rs761097752 · VCV2195219
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.043 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.88 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 13.69 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,906 alleles
Filtering AF
0.0005%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000366%
Overall
0.000993%
16/1,611,802 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,453 |
| Admixed American | 0.00167% | 59,998 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,454 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000932% | 107,261 |
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.Ser147=
- Coding
- c.441G>A
- MANE Select
- NM_001283
- dbSNP
- rs761097752
- Type
- single nucleotide variant
- Location
- chr7:101160530 (GRCh38)
- Gene constraint
- LOEUF 1.078 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.83 · 1 PDB
- Residue 147
- a modified residue (phosphoserine)
Similar variants
- AP1S1 p.Ser147Leu Uncertain significance ★ ⚠ same residue
- 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
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-ser147 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown