Is AP4B1 c.667del pathogenic?

AP4B1 c.667del is classified Pathogenic in AP4B1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2014-07-01). Absent from gnomAD; Associated with hereditary spastic paraplegia 47.

What condition is associated with AP4B1 c.667del?

AP4B1 c.667del is associated with hereditary spastic paraplegia 47 (ClinVar).

How common is AP4B1 c.667del in the general population?

AP4B1 c.667del is absent from gnomAD (gnomAD).

AP4B1 c.667del

Q: How is Severe intellectual disability and progressive spastic paraplegia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

rs2101027843 · VCV209982

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary spastic paraplegia 47

Computational evidence

Protein change
Missense predictors do not apply to this variant type.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AP4B1
Coding: c.667del
MANE Select: NM_001253852 · reported on NM_006594
dbSNP: rs2101027843
Type: Deletion
Gene constraint: LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.56 · 5 PDB

Full AP4B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 47 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe intellectual disability and progressive spastic paraplegia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

AP4B1 p.Gln331fs Pathogenic/Likely pathogenic ★★ same condition
AP4B1 p.Thr387fs Pathogenic/Likely pathogenic ★★ same condition
AP4B1 p.Tyr135_Arg137delinsTer Pathogenic ★★ same condition
AP4B1 c.1106_1114+8del Likely pathogenic ★ same condition
AP4B1 p.Ala105fs Pathogenic ★ same condition
AP4B1 p.Arg497fs Pathogenic ★ same condition
AP4B1 p.Cys356fs Likely pathogenic ★ same condition
AP4B1 p.Gly309fs 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-c-667del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown