Is AP3B1 p.Ala630= (c.1890T>C) pathogenic?

AP3B1 p.Ala630= (c.1890T>C) is classified Conflicting classifications of pathogenicity in AP3B1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-18). Very rare (popmax 0.000254%, nfe); Associated with Hermansky-Pudlak syndrome 2.

What condition is associated with AP3B1 p.Ala630= (c.1890T>C)?

AP3B1 p.Ala630= (c.1890T>C) is associated with Hermansky-Pudlak syndrome 2 (ClinVar).

How common is AP3B1 p.Ala630= (c.1890T>C) in the general population?

AP3B1 p.Ala630= (c.1890T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

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

AP3B1 p.Ala630=

c.1890T>C · rs774196917 · VCV764149

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, 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 0.22	GERP -0.046, phastCons 0.013
Overall
CADD	4.979	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,146 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,460,840 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: AP3B1
Protein: p.Ala630=
Coding: c.1890T>C
MANE Select: NM_003664
dbSNP: rs774196917
Type: single nucleotide variant
Location: chr5:78128108 (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-ala630 (accessed [today's date]).

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