Is AP4B1 p.Pro308= (c.924A>G) pathogenic?

AP4B1 p.Pro308= (c.924A>G) is classified Conflicting classifications of pathogenicity in AP4B1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-04-06). Very rare (popmax 0.00223%, eas); Associated with hereditary spastic paraplegia.

What condition is associated with AP4B1 p.Pro308= (c.924A>G)?

AP4B1 p.Pro308= (c.924A>G) is associated with hereditary spastic paraplegia, hereditary spastic paraplegia 47 (ClinVar).

How common is AP4B1 p.Pro308= (c.924A>G) in the general population?

AP4B1 p.Pro308= (c.924A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

AP4B1 p.Pro308=

c.924A>G · rs1256078127 · VCV1343960

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -10	GERP -4.5
Overall
CADD	0.518	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,892 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,892
European (non-Finnish)	0.000593%	168,578

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.Pro308=
Coding: c.924A>G
dbSNP: rs1256078127
Type: single nucleotide variant
Location: chr1:113900094 (GRCh38)

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

Disease context

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

Also linked: hereditary spastic paraplegia 47

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-pro308 (accessed [today's date]).

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