Is AP3B2 p.Arg442Ter (c.1324C>T) pathogenic?

AP3B2 p.Arg442Ter (c.1324C>T) is classified Likely pathogenic in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). Very rare (popmax 0.00339%, amr); Associated with developmental and epileptic encephalopathy, 48.

What condition is associated with AP3B2 p.Arg442Ter (c.1324C>T)?

AP3B2 p.Arg442Ter (c.1324C>T) is associated with developmental and epileptic encephalopathy, 48 (ClinVar).

How common is AP3B2 p.Arg442Ter (c.1324C>T) in the general population?

AP3B2 p.Arg442Ter (c.1324C>T) is very rare (popmax 0.00339%, amr) (gnomAD).

AP3B2 p.Arg442Ter

c.1324C>T · VCV4851448

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00339%, amr)

Conditions

developmental and epileptic encephalopathy, 48

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 27
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP -3.8, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00339% Admixed American · 2/59,040 alleles

Filtering AF 0.000562% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00021%

Overall 0.000275% 4/1,454,742 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00339%	29,520
European (non-Finnish)	0.00017%	588,433

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.Arg442Ter
Coding: c.1324C>T
MANE Select: NM_001278512
Type: single nucleotide variant
Location: chr15:82677725 (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-arg442ter (accessed [today's date]).

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