Is AP3B1 p.Ala170= (c.510A>C) pathogenic?

AP3B1 p.Ala170= (c.510A>C) is classified Likely benign in AP3B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). Very rare (popmax 0.000593%, nfe); Associated with Hermansky-Pudlak syndrome 2.

What condition is associated with AP3B1 p.Ala170= (c.510A>C)?

AP3B1 p.Ala170= (c.510A>C) is associated with Hermansky-Pudlak syndrome 2 (ClinVar).

How common is AP3B1 p.Ala170= (c.510A>C) in the general population?

AP3B1 p.Ala170= (c.510A>C) is very rare (popmax 0.000593%, nfe) (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

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

AP3B1 p.Ala170=

c.510A>C · VCV4766668

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Conditions

Hermansky-Pudlak syndrome 2

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 0.7	GERP -5.5, phastCons 1
Overall
CADD	10.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,179,728 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000547% 8/1,461,374 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)grpmax	0.000593%	168,533

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: AP3B1
Protein: p.Ala170=
Coding: c.510A>C
MANE Select: NM_003664
Type: single nucleotide variant
Location: chr5:78227398 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.85 · 5 PDB

Full AP3B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hermansky-Pudlak syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial hemophagocytic lymphohistiocytosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Infancy
Prevalence: 1-9 / 100 000 (Sweden)

Similar variants

AP3B1 c.2078-1G>A Likely pathogenic ★★ same condition
AP3B1 c.280-2A>G Likely pathogenic ★★ same condition
AP3B1 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same condition
AP3B1 p.Arg649Ter Pathogenic/Likely pathogenic ★★ same condition
AP3B1 c.128+4A>G Uncertain significance ★★ same condition
AP3B1 c.2077+6T>C Uncertain significance ★★ same condition
AP3B1 c.2809+4A>G Uncertain significance ★★ same condition
AP3B1 c.2992+3G>A 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/ap3b1-p-ala170 (accessed [today's date]).

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