Is AP4B1 p.Glu190= (c.570A>G) pathogenic?

AP4B1 p.Glu190= (c.570A>G) is classified Likely benign in AP4B1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-12). Rare (popmax 0.164%, afr); Associated with Inborn genetic diseases.

What condition is associated with AP4B1 p.Glu190= (c.570A>G)?

AP4B1 p.Glu190= (c.570A>G) is associated with Inborn genetic diseases, hereditary spastic paraplegia 47 (ClinVar).

How common is AP4B1 p.Glu190= (c.570A>G) in the general population?

AP4B1 p.Glu190= (c.570A>G) is rare (popmax 0.164%, afr) (gnomAD).

AP4B1 p.Glu190=

c.570A>G · rs139775124 · VCV588790

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.164%, afr)

Conditions

Inborn genetic diseases

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 2.8	GERP 1.1, phastCons 1
Overall
CADD	12.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.164% African / African-American · 123/75,042 alleles

Filtering AF 0.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.00867% 140/1,614,176 alleles · rare exomes 70/1,461,874 · genomes 70/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.164%	610
Remaining individualsnot grpmax-eligible	0.016%	6,251
Admixed American	0.0117%	8,573

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.Glu190=
Coding: c.570A>G
MANE Select: NM_001253852
dbSNP: rs139775124
Type: single nucleotide variant
Location: chr1:113901283 (GRCh38)
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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 47

Similar variants

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
AP4B1 p.Arg514Ter 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-glu190 (accessed [today's date]).

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