Is AP1G1 p.Ala709= (c.2127A>G) pathogenic?

AP1G1 p.Ala709= (c.2127A>G) is classified Likely benign in AP1G1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-18). Ultra-rare (popmax 0.0386%, afr); Associated with AP1G1-related disorder.

What condition is associated with AP1G1 p.Ala709= (c.2127A>G)?

AP1G1 p.Ala709= (c.2127A>G) is associated with AP1G1-related disorder (ClinVar).

How common is AP1G1 p.Ala709= (c.2127A>G) in the general population?

AP1G1 p.Ala709= (c.2127A>G) is ultra-rare (popmax 0.0386%, afr) (gnomAD).

AP1G1 p.Ala709=

c.2127A>G · VCV3357825

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0386%, afr)

Conditions

AP1G1-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 -3.3	GERP -4.6
Overall
CADD	7.585	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0386% African / African-American · 29/75,056 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0238%

Overall 0.00279% 45/1,614,228 alleles · ultra-rare exomes 25/1,461,878 · genomes 20/152,350 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0386%	2,588
Remaining individualsnot grpmax-eligible	0.0096%	10,419
South Asian	0.00329%	30,363
East Asian	0.00223%	44,882
Admixed American	0.00167%	60,024
European (non-Finnish)	0.000424%	236,007

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: AP1G1
Protein: p.Ala709=
Coding: c.2127A>G
MANE Select: NM_001128
Type: single nucleotide variant
Location: chr16:71739083 (GRCh38)
Gene constraint: LOEUF 0.113 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.56 · 1 PDB
Residue 709: the gae domain; a β-strand

Full AP1G1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AP1G1-related disorder

Similar variants

AP1G1 p.Arg424Leu Uncertain significance ★ ⚠ same condition
AP1G1 p.Gly66Glu Uncertain significance ★ ⚠ same condition
AP1G1 p.Lys783Glu Uncertain significance ★ ⚠ same condition
AP1G1 p.Ser518Cys Uncertain significance ★ ⚠ same condition
AP1G1 p.Val99Ala Uncertain significance ★ ⚠ same condition
AP1G1 p.Arg48Trp Uncertain significance ⚠ same condition
AP1G1 p.Arg523Ter Uncertain significance same condition
AP1G1 c.1999+2dup 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/ap1g1-p-ala709 (accessed [today's date]).

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