AP4B1 p.Asp432=
c.1296T>C · VCV4764813
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
hereditary spastic paraplegia 47
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.44 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.58 | GERP -4.3, phastCons 0.001 |
| Overall | ||
| CADD | 8.908 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- AP4B1
- Protein
- p.Asp432=
- Coding
- c.1296T>C
- MANE Select
- NM_001253852
- Type
- single nucleotide variant
- Location
- chr1:113897846 (GRCh38)
- Gene constraint
- LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.56 · 5 PDB
Disease context
hereditary spastic paraplegia 47 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Severe intellectual disability and progressive spastic paraplegia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- AP4B1 p.Asp432Asn Uncertain significance ★★ ⚠ same residue
- AP4B1 c.114-2A>C Pathogenic ★★ same condition
- AP4B1 c.114-2A>G Pathogenic ★★ same condition
- AP4B1 p.Arg102Ter Pathogenic ★★ same condition
- AP4B1 p.Arg206Ter Pathogenic/Likely pathogenic ★★ same condition
- AP4B1 p.Arg353Ter Pathogenic/Likely pathogenic ★★ same condition
- AP4B1 p.Arg393Ter Pathogenic ★★ same condition
- AP4B1 p.Arg406Ter Pathogenic/Likely pathogenic ★★ 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/ap4b1-p-asp432 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown