Is AP3B2 p.Asp699fs (c.2095dup) pathogenic?

AP3B2 p.Asp699fs (c.2095dup) is classified Pathogenic in AP3B2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-30). Very rare (popmax 0.0017%, amr).

How common is AP3B2 p.Asp699fs (c.2095dup) in the general population?

AP3B2 p.Asp699fs (c.2095dup) is very rare (popmax 0.0017%, amr) (gnomAD).

AP3B2 p.Asp699fs

c.2095dup · rs1391900515 · VCV2982388

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 18 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0017% Admixed American · 1/58,714 alleles

Overall 6.89e-05% 1/1,452,308 alleles · very rare

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.Asp699fs
Coding: c.2095dup
MANE Select: NM_001278512
dbSNP: rs1391900515
Type: Duplication
Location: chr15:82664876 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 75.73
Residue 699: the 'disordered' region

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

Similar variants

AP3B2 p.Met322_Ala325dup Uncertain significance ★★ same type
AP3B2 p.Asn1039fs Pathogenic ★ same type
AP3B2 p.Asp301fs Pathogenic ★ same type
AP3B2 p.Cys683fs Pathogenic ★ same type
AP3B2 p.Ser292fs Pathogenic ★ same type
AP3B2 p.Ser818fs Pathogenic ★ same type
AP3B2 p.Tyr160Ter Pathogenic ★ same type
AP3B2 c.2497+2dup Uncertain significance ★ same type

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-asp699fs (accessed [today's date]).

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