Is AP3D1 p.Arg856fs (c.2567_2570del) pathogenic?

AP3D1 p.Arg856fs (c.25672570del) is classified Uncertain significance in AP3D1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). Very rare (popmax 8.64e-05%, nfe).

How common is AP3D1 p.Arg856fs (c.2567_2570del) in the general population?

AP3D1 p.Arg856fs (c.2567_2570del) is very rare (popmax 8.64e-05%, nfe) (gnomAD).

AP3D1 p.Arg856fs

c.2567_2570del · rs2512147328 · VCV1967527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.64e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 22 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.1	GERP -2.2
Region caveats
Repeat context	tandem	(TTCTCT)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.64e-05% European (non-Finnish) · 1/1,156,942 alleles

Overall 7.05e-05% 1/1,417,618 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: AP3D1
Protein: p.Arg856fs
Coding: c.2567_2570del
MANE Select: NM_001261826
dbSNP: rs2512147328
Type: Microsatellite
Location: chr19:2114156 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 6 PDB
Residue 856: the 'disordered' region

Full AP3D1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AP3D1 p.Arg856Lys Uncertain significance ★ ⚠ same residue
AP3D1 p.882AP[2] Uncertain significance ★★ same type
AP3D1 p.882AP[3] Uncertain significance ★★ same type
AP3D1 p.Leu987del Uncertain significance ★★ same type
AP3D1 p.863EK[1] Conflicting classifications of pathogenicity ★ same type
AP3D1 p.882AP[5] Conflicting classifications of pathogenicity ★ same type
AP3D1 p.Gln977dup Uncertain significance ★ same type
AP3D1 p.Lys861_Lys862del 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/ap3d1-p-arg856fs (accessed [today's date]).

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