Is AP3D1 p.Val1189fs (c.3565_3566del) pathogenic?

AP3D1 p.Val1189fs (c.35653566del) is classified Pathogenic in AP3D1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-07-27). Absent from gnomAD; Associated with Hermansky-Pudlak syndrome 10.

What condition is associated with AP3D1 p.Val1189fs (c.3565_3566del)?

AP3D1 p.Val1189fs (c.3565_3566del) is associated with Hermansky-Pudlak syndrome 10 (ClinVar).

How common is AP3D1 p.Val1189fs (c.3565_3566del) in the general population?

AP3D1 p.Val1189fs (c.3565_3566del) is absent from gnomAD (gnomAD).

How is Hermansky-Pudlak syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

AP3D1 p.Val1189fs

c.3565_3566del · rs879255646 · VCV253144

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Hermansky-Pudlak syndrome 10

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	escapes	premature termination codon in the last exon (32 of 32) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.51	GERP -2.3, phastCons 0.032

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AP3D1
Protein: p.Val1189fs
Coding: c.3565_3566del
MANE Select: NM_001261826
dbSNP: rs879255646
Type: Deletion
Location: chr19:2102255 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 6 PDB

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

Disease context

Hermansky-Pudlak syndrome 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hermansky-Pudlak syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

AP3D1 c.1803_1859+5del Uncertain significance ★ same condition
AP3D1 p.Val1189Phe Uncertain significance ★ ⚠ same residue
AP3D1 c.2001+6C>T Uncertain significance ★★ same condition
AP3D1 c.2601+6G>T Uncertain significance ★★ same condition
AP3D1 p.Ala1213Thr Uncertain significance ★★ ⚠ same condition
AP3D1 p.Ala455Thr Uncertain significance ★★ ⚠ same condition
AP3D1 p.Arg117Cys Uncertain significance ★★ ⚠ same condition
AP3D1 p.Cys1165Gly 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/ap3d1-p-val1189fs (accessed [today's date]).

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