AP1S2 p.Glu124=
c.372A>G · VCV4849140
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000447%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.151 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.2 | GERP -0.56, phastCons 1 |
| Overall | ||
| CADD | 8.126 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000447%
European (non-Finnish) · 4/894,766 alleles
Filtering AF
0.000105%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 7.1e-05%
Overall
0.000331%
4/1,208,286 alleles · very rare
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
- AP1S2
- Protein
- p.Glu124=
- Coding
- c.372A>G
- MANE Select
- NM_001272071
- Type
- single nucleotide variant
- Location
- chrX:15845433 (GRCh38)
- Structure
- AlphaFold pLDDT 94.36
Similar variants
- AP1S2 c.-1+1G>A Pathogenic/Likely pathogenic ★★ same type
- AP1S2 p.Arg52Ter Pathogenic ★★ same type
- AP1S2 p.Gln123Ter Pathogenic ★★ same type
- AP1S2 p.Asn129Thr Uncertain significance ★★ ⚠ same type
- AP1S2 p.Gly158Arg Uncertain significance ★★ ⚠ same type
- AP1S2 p.Ile134Thr Uncertain significance ★★ ⚠ same type
- AP1S2 p.Ile82Val Uncertain significance ★★ ⚠ same type
- AP1S2 p.Leu54Val Uncertain significance ★★ ⚠ 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/ap1s2-p-glu124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown