AP4B1 p.Ser323=
c.969G>A · VCV4906822
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.99 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.86 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.051 | GERP -0.66, phastCons 0.69 |
| Overall | ||
| CADD | 24.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,082 alleles
Filtering AF
0.000878%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000717%
Overall
0.0013%
21/1,614,000 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,361 |
| European (non-Finnish) | 0.00144% | 69,414 |
| African / African-American | 0.00134% | 74,878 |
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
- AP4B1
- Protein
- p.Ser323=
- Coding
- c.969G>A
- MANE Select
- NM_001253852
- Type
- single nucleotide variant
- Location
- chr1:113900049 (GRCh38)
- Gene constraint
- LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.56 · 5 PDB
Similar variants
- AP4B1 p.Ser323Thr Uncertain significance ★★ ⚠ same residue
- AP4B1 p.Ser323Leu Benign ★★ ⚠ same residue
- AP4B1 p.Ser323fs Pathogenic same residue
- AP4B1 c.114-2A>C Pathogenic ★★ same type
- AP4B1 c.114-2A>G Pathogenic ★★ same type
- AP4B1 p.Arg102Ter Pathogenic ★★ same type
- AP4B1 p.Arg206Ter Pathogenic/Likely pathogenic ★★ same type
- AP4B1 p.Arg353Ter Pathogenic/Likely pathogenic ★★ 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/ap4b1-p-ser323 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown