Is AP4B1 p.Pro552fs (c.1655del) pathogenic?

AP4B1 p.Pro552fs (c.1655del) is classified Likely pathogenic in AP4B1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-10-01). Absent from gnomAD; Associated with Spastic paraplegia.

What condition is associated with AP4B1 p.Pro552fs (c.1655del)?

AP4B1 p.Pro552fs (c.1655del) is associated with Spastic paraplegia (ClinVar).

How common is AP4B1 p.Pro552fs (c.1655del) in the general population?

AP4B1 p.Pro552fs (c.1655del) is absent from gnomAD (gnomAD).

AP4B1 p.Pro552fs

c.1655del · rs2100994885 · VCV1344780

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.12	GERP -4.2, phastCons 0.12

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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
Protein: p.Pro552fs
Coding: c.1655del
MANE Select: NM_001253852
dbSNP: rs2100994885
Type: Deletion
Location: chr1:113895894 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.56 · 5 PDB
Residue 552: the 'hinge' region

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

Disease context

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

Similar variants

AP4B1 p.Asn452fs Likely pathogenic same condition
AP4B1 p.Leu104fs Likely pathogenic same condition
AP4B1 p.Leu499fs Likely pathogenic same condition
AP4B1 p.Arg137Gly Likely pathogenic same condition
AP4B1 p.Gln331Ter Likely pathogenic same condition
AP4B1 p.Lys537fs Likely pathogenic same condition
AP4B1 p.Gln331fs Pathogenic/Likely pathogenic ★★ same type
AP4B1 p.Thr387fs 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-pro552fs (accessed [today's date]).

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