Is AP4B1 p.Arg482His (c.1445G>A) pathogenic?

AP4B1 p.Arg482His (c.1445G>A) is classified Uncertain significance in AP4B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely benign (0.0864); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with AP4B1 p.Arg482His (c.1445G>A)?

AP4B1 p.Arg482His (c.1445G>A) is associated with Inborn genetic diseases (ClinVar).

How common is AP4B1 p.Arg482His (c.1445G>A) in the general population?

AP4B1 p.Arg482His (c.1445G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about AP4B1 p.Arg482His (c.1445G>A)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

AP4B1 p.Arg482His

c.1445G>A · VCV3404415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -10.13	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 9,649 bp · p 0.84 · regional, not allelic
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.00615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00573%

Overall 0.00595% 96/1,614,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
European (non-Finnish)	0.00746%	13,410
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00267%	37,456
Admixed American	0.00167%	60,002

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.Arg482His
Coding: c.1445G>A
MANE Select: NM_001253852
Type: single nucleotide variant
Location: chr1:113896323 (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

Similar variants

AP4B1 p.Arg482Cys Uncertain significance ★ ⚠ same residue
AP4B1 c.114-2A>G Pathogenic ★★ same condition
AP4B1 c.470-6T>G Uncertain significance ★★ same condition
AP4B1 p.Ala361Val Uncertain significance ★★ ⚠ same condition
AP4B1 p.Ala83Pro Uncertain significance ★★ ⚠ same condition
AP4B1 p.Arg130Gln Uncertain significance ★★ ⚠ same condition
AP4B1 p.Arg169His Uncertain significance ★★ ⚠ same condition
AP4B1 p.Arg224Cys Uncertain significance ★★ ⚠ 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-arg482his (accessed [today's date]).

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