Is AP3B2 p.Asp893Glu (c.2679C>G) pathogenic?

AP3B2 p.Asp893Glu (c.2679C>G) is classified Uncertain significance in AP3B2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-06-03). AlphaMissense: likely benign (0.1176); Very rare (popmax 0.00935%, afr); Associated with developmental and epileptic encephalopathy, 48.

What condition is associated with AP3B2 p.Asp893Glu (c.2679C>G)?

AP3B2 p.Asp893Glu (c.2679C>G) is associated with developmental and epileptic encephalopathy, 48 (ClinVar).

How common is AP3B2 p.Asp893Glu (c.2679C>G) in the general population?

AP3B2 p.Asp893Glu (c.2679C>G) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about AP3B2 p.Asp893Glu (c.2679C>G)?

AlphaMissense predicts likely benign (score 0.1176) — an in-silico prediction, not a clinical call.

AP3B2 p.Asp893Glu

c.2679C>G · rs757342482 · VCV1034107

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1176 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy, 48

Computational evidence

Protein change
AlphaMissense	0.1176	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.16	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 2.6	GERP 0.87, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,925 bp · p 0.51 · regional, not allelic
Overall
CADD	16.27	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 D874E vs ClinVar D893E) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,906 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00062% 10/1,613,576 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,701
Admixed American	0.00167%	59,948
European (non-Finnish)	0.00017%	589,904

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.Asp893Glu
Coding: c.2679C>G
MANE Select: NM_001278512
dbSNP: rs757342482
Type: single nucleotide variant
Location: chr15:82662848 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73

Full AP3B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 48 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AP3B2 p.Arg977Ter Pathogenic ★★ same condition
AP3B2 p.Gln839Ter Pathogenic/Likely pathogenic ★★ same condition
AP3B2 c.1110+3G>C Uncertain significance ★★ same condition
AP3B2 p.Ala1098Asp Uncertain significance ★★ ⚠ same condition
AP3B2 p.Ala546Pro Uncertain significance ★★ ⚠ same condition
AP3B2 p.Arg977Gln Uncertain significance ★★ ⚠ same condition
AP3B2 p.Arg99Cys Uncertain significance ★★ ⚠ same condition
AP3B2 p.Asn552Tyr 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-asp893glu (accessed [today's date]).

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