Is AP3B2 p.Ser783= (c.2349C>T) pathogenic?

AP3B2 p.Ser783= (c.2349C>T) is classified Likely benign in AP3B2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Rare (popmax 0.123%, nfe); Associated with developmental and epileptic encephalopathy, 48.

What condition is associated with AP3B2 p.Ser783= (c.2349C>T)?

AP3B2 p.Ser783= (c.2349C>T) is associated with developmental and epileptic encephalopathy, 48 (ClinVar).

How common is AP3B2 p.Ser783= (c.2349C>T) in the general population?

AP3B2 p.Ser783= (c.2349C>T) is rare (popmax 0.123%, nfe) (gnomAD).

AP3B2 p.Ser783=

c.2349C>T · rs143109436 · VCV733385

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.123%, nfe)

Conditions

developmental and epileptic encephalopathy, 48

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 -6.8	GERP -3.4
Overall
CADD	0.484	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% European (non-Finnish) · 1,456/1,179,852 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.0996% 1,607/1,613,588 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.123%	810
Remaining individualsnot grpmax-eligible	0.107%	933
Admixed American	0.0917%	1,091
Middle Eastern	0.066%	1,516
African / African-American	0.0133%	7,505
South Asian	0.00988%	10,118
East Asian	0.00668%	14,959
Finnishnot grpmax-eligible	0.00471%	21,229

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.Ser783=
Coding: c.2349C>T
MANE Select: NM_001278512
dbSNP: rs143109436
Type: single nucleotide variant
Location: chr15:82663888 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 783: the 'disordered' region

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-ser783 (accessed [today's date]).

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