Is AP1B1 p.Ala609= (c.1827C>G) pathogenic?

AP1B1 p.Ala609= (c.1827C>G) is classified Likely benign in AP1B1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-03). Rare (popmax 0.272%, nfe); Associated with AP1B1-related disorder.

What condition is associated with AP1B1 p.Ala609= (c.1827C>G)?

AP1B1 p.Ala609= (c.1827C>G) is associated with AP1B1-related disorder (ClinVar).

How common is AP1B1 p.Ala609= (c.1827C>G) in the general population?

AP1B1 p.Ala609= (c.1827C>G) is rare (popmax 0.272%, nfe) (gnomAD).

AP1B1 p.Ala609=

c.1827C>G · rs139231493 · VCV3049847

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.272%, nfe)

Conditions

AP1B1-related disorder

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	GERP 0.58, phastCons 1
Overall
CADD	7.119	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.272% European (non-Finnish) · 3,191/1,174,186 alleles

Filtering AF 0.264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.261%

Overall 0.223% 3,560/1,598,434 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.272%	367
European (non-Finnish)grpmax	0.272%	368
Remaining individualsnot grpmax-eligible	0.195%	512
Admixed American	0.0791%	1,264
African / African-American	0.0347%	2,883
Middle Eastern	0.0177%	5,648
South Asian	0.00571%	17,521

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: AP1B1
Protein: p.Ala609=
Coding: c.1827C>G
MANE Select: NM_001127
dbSNP: rs139231493
Type: single nucleotide variant
Location: chr22:29340827 (GRCh38)
Gene constraint: LOEUF 0.476 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 82.46 · 20 PDB
Residue 609: the 'disordered' region

Full AP1B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AP1B1-related disorder

Similar variants

AP1B1 p.Gly643Ser Uncertain significance ⚠ same condition
AP1B1 c.2164-8C>T Likely benign same condition
AP1B1 c.2309+8C>T Likely benign same condition
AP1B1 c.2524+5G>A Likely benign same condition
AP1B1 c.*7G>A Likely benign same condition
AP1B1 p.Ala373= Likely benign same condition
AP1B1 p.Ala87= Likely benign same condition
AP1B1 p.Arg235His Likely benign ⚠ 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/ap1b1-p-ala609 (accessed [today's date]).

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