AP4B1 p.Asp358=
c.1074T>C · rs2101024006 · VCV1675369
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -4.5 |
| Overall | ||
| CADD | 1.046 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,180,040 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000205%
3/1,461,892 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
- AP4B1
- Protein
- p.Asp358=
- Coding
- c.1074T>C
- MANE Select
- NM_001253852
- dbSNP
- rs2101024006
- Type
- single nucleotide variant
- Location
- chr1:113899944 (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 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
- AP4B1 p.Arg393Ter Pathogenic ★★ same type
- AP4B1 p.Arg406Ter Pathogenic/Likely pathogenic ★★ same type
- AP4B1 p.Arg514Ter 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-asp358 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown