AP1B1 p.Ala373=
c.1119T>C · VCV3358172
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00831%, nfe)
Conditions
1
AP1B1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.144 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.43 | GERP 0.84 |
| Overall | ||
| CADD | 9.781 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00831%
European (non-Finnish) · 98/1,179,882 alleles
Filtering AF
0.00697%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.0062%
100/1,613,896 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00831% | 12,040 |
| Admixed American | 0.00167% | 60,006 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
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
- AP1B1
- Protein
- p.Ala373=
- Coding
- c.1119T>C
- MANE Select
- NM_001127
- Type
- single nucleotide variant
- Location
- chr22:29351207 (GRCh38)
- Gene constraint
- LOEUF 0.476 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 82.46 · 20 PDB
- Residue 373
- an α-helix
Disease context
AP1B1-related disorder
Similar variants
- AP1B1 p.Gly643Ser Uncertain significance ⚠ same condition
- AP1B1 c.2164-8C>T Likely benign same condition
- AP1B1 c.2309+8C>T Likely benign same condition
- AP1B1 c.2524+5G>A Likely benign same condition
- AP1B1 c.*7G>A Likely benign same condition
- AP1B1 p.Ala609= Likely benign same condition
- AP1B1 p.Ala87= Likely benign same condition
- AP1B1 p.Arg235His Likely benign ⚠ same condition
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/ap1b1-p-ala373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown