Is AP3B2 p.Glu799Asp (c.2397G>C) pathogenic?

AP3B2 p.Glu799Asp (c.2397G>C) is classified Uncertain significance in AP3B2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-19). AlphaMissense: likely benign (0.0796); Ultra-rare (popmax 0.0493%, mid); Associated with Inborn genetic diseases.

What condition is associated with AP3B2 p.Glu799Asp (c.2397G>C)?

AP3B2 p.Glu799Asp (c.2397G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AP3B2 p.Glu799Asp (c.2397G>C) in the general population?

AP3B2 p.Glu799Asp (c.2397G>C) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about AP3B2 p.Glu799Asp (c.2397G>C)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

AP3B2 p.Glu799Asp

c.2397G>C · rs200655723 · VCV1350927

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -6.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.023	GERP 0.58, phastCons 0.73
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	12.96	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E780D vs ClinVar E799D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00328% 53/1,613,792 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
South Asian	0.00769%	13,008
European (non-Finnish)	0.00347%	28,777
Remaining individualsnot grpmax-eligible	0.0016%	62,460
African / African-American	0.00133%	74,936

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: AP3B2
Protein: p.Glu799Asp
Coding: c.2397G>C
MANE Select: NM_001278512
dbSNP: rs200655723
Type: single nucleotide variant
Location: chr15:82663840 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 799: the 'disordered' region

Full AP3B2 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

AP3B2 p.Glu799Gly Uncertain significance ★ ⚠ same residue
AP3B2 p.Glu799Lys Uncertain significance ★ ⚠ same residue
AP3B2 c.2834-3C>A Uncertain significance ★★ same condition
AP3B2 p.Ala1076Pro Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala1098Asp Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala4Val Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala633Val Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala710Thr 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/ap3b2-p-glu799asp (accessed [today's date]).

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