Is AP3B1 p.Ala960= (c.2880C>T) pathogenic?

AP3B1 p.Ala960= (c.2880C>T) is classified Benign/Likely benign in AP3B1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-31). Rare (popmax 0.348%, nfe); Associated with autoinflammatory syndrome.

What condition is associated with AP3B1 p.Ala960= (c.2880C>T)?

AP3B1 p.Ala960= (c.2880C>T) is associated with autoinflammatory syndrome, Hermansky-Pudlak syndrome 2 (ClinVar).

How common is AP3B1 p.Ala960= (c.2880C>T) in the general population?

AP3B1 p.Ala960= (c.2880C>T) is rare (popmax 0.348%, nfe) (gnomAD).

AP3B1 p.Ala960=

c.2880C>T · rs62001052 · VCV354223

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.348%, nfe)

Conditions

autoinflammatory syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.04	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.3, phastCons 1
Overall
CADD	9.556	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.348% European (non-Finnish) · 4,100/1,177,566 alleles

Filtering AF 0.339% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.336%

Overall 0.371% 5,976/1,611,118 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.6%	38
European (non-Finnish)grpmax	0.348%	287
Remaining individualsnot grpmax-eligible	0.274%	365
African / African-American	0.0467%	2,140
Admixed American	0.00667%	14,996

Finnish 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.Ala960=
Coding: c.2880C>T
MANE Select: NM_003664
dbSNP: rs62001052
Type: single nucleotide variant
Location: chr5:78034375 (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 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-ala960 (accessed [today's date]).

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