Is AP3B1 p.His871= (c.2613C>T) pathogenic?

AP3B1 p.His871= (c.2613C>T) is classified Benign/Likely benign in AP3B1 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-02). Rare (popmax 0.857%, sas); Associated with autoinflammatory syndrome.

What condition is associated with AP3B1 p.His871= (c.2613C>T)?

AP3B1 p.His871= (c.2613C>T) is associated with autoinflammatory syndrome, Hermansky-Pudlak syndrome 2 (ClinVar).

How common is AP3B1 p.His871= (c.2613C>T) in the general population?

AP3B1 p.His871= (c.2613C>T) is rare (popmax 0.857%, sas) (gnomAD).

AP3B1 p.His871=

c.2613C>T · rs144420604 · VCV210188

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.857%, sas)

Conditions

autoinflammatory syndrome

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 -1.2	GERP -5.6
Overall
CADD	0.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.857% South Asian · 781/91,088 alleles

Filtering AF 0.807% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.788%

Overall 0.452% 7,296/1,614,106 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.857%	117
Finnishnot grpmax-eligible	0.506%	198
European (non-Finnish)	0.487%	205
Remaining individualsnot grpmax-eligible	0.394%	254
Middle Eastern	0.379%	264
Admixed American	0.195%	513
African / African-American	0.0653%	1,531
East Asian	0.0245%	4,079
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.His871=
Coding: c.2613C>T
MANE Select: NM_003664
dbSNP: rs144420604
Type: single nucleotide variant
Location: chr5:78039239 (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

autoinflammatory syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Hermansky-Pudlak syndrome 2

Similar variants

AP3B1 p.His871Asp Uncertain significance ★★ ⚠ same residue
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

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-his871 (accessed [today's date]).

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