AP4B1 p.Cys73=
c.219C>T · rs2101044378 · VCV2582859
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000424%, 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 3 | GERP 0.14, phastCons 1 |
| Overall | ||
| CADD | 10.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000424%
European (non-Finnish) · 5/1,180,028 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000342%
5/1,461,882 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.Cys73=
- Coding
- c.219C>T
- MANE Select
- NM_001253852
- dbSNP
- rs2101044378
- Type
- single nucleotide variant
- Location
- chr1:113902757 (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.Cys73Ser Uncertain significance ★★ ⚠ same residue
- AP4B1 p.Cys73Ter 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
- AP4B1 p.Arg393Ter 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-cys73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown