Is ARFGAP2 p.Ala266= (c.798G>A) pathogenic?

ARFGAP2 p.Ala266= (c.798G>A) is classified Benign in ARFGAP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-04). Low-frequency (popmax 1.99%, afr); Associated with ARFGAP2-related disorder.

What condition is associated with ARFGAP2 p.Ala266= (c.798G>A)?

ARFGAP2 p.Ala266= (c.798G>A) is associated with ARFGAP2-related disorder (ClinVar).

How common is ARFGAP2 p.Ala266= (c.798G>A) in the general population?

ARFGAP2 p.Ala266= (c.798G>A) is low-frequency (popmax 1.99%, afr) (gnomAD).

ARFGAP2 p.Ala266=

c.798G>A · rs34580829 · VCV3045780

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.99%, afr)

Conditions

ARFGAP2-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 -20	GERP -5
Overall
CADD	0.009	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.99% African / African-American · 1,493/75,052 alleles

Filtering AF 1.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.87%

Overall 0.108% 1,736/1,613,754 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.99%	50
Admixed American	0.163%	613
Remaining individualsnot grpmax-eligible	0.162%	619
Middle Eastern	0.115%	866
South Asian	0.00439%	22,772
European (non-Finnish)	0.0028%	35,759

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: ARFGAP2
Protein: p.Ala266=
Coding: c.798G>A
MANE Select: NM_032389
dbSNP: rs34580829
Type: single nucleotide variant
Location: chr11:47171675 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.19 · 1 PDB
Residue 266: the 'required for interaction with coatomer' region

Full ARFGAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARFGAP2-related disorder

Similar variants

ARFGAP2 p.Ala266Val Uncertain significance ★ ⚠ same residue
ARFGAP2 c.191+6C>T Likely benign same condition
ARFGAP2 c.265-10T>C Likely benign same condition
ARFGAP2 c.396+7G>A Likely benign same condition
ARFGAP2 c.809+6T>C Benign same condition
ARFGAP2 c.-9G>A Likely benign same condition
ARFGAP2 c.*4G>A Benign same condition
ARFGAP2 p.Arg255Cys 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/arfgap2-p-ala266 (accessed [today's date]).

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