Is ARFGAP2 p.Glu289Gly (c.866A>G) pathogenic?

ARFGAP2 p.Glu289Gly (c.866A>G) is classified Uncertain significance in ARFGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.2446); Absent from gnomAD v4.1.

How common is ARFGAP2 p.Glu289Gly (c.866A>G) in the general population?

ARFGAP2 p.Glu289Gly (c.866A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARFGAP2 p.Glu289Gly (c.866A>G)?

AlphaMissense predicts likely benign (score 0.2446) — an in-silico prediction, not a clinical call.

ARFGAP2 p.Glu289Gly

c.866A>G · rs2540297819 · VCV3128344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2446 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2446	likely benign
REVEL	0.275	benign-leaning
SaProt	LLR -9.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.89 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.12 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARFGAP2
Protein: p.Glu289Gly
Coding: c.866A>G
MANE Select: NM_032389
dbSNP: rs2540297819
Type: single nucleotide variant
Location: chr11:47171501 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.19 · 1 PDB
Residue 289: the 'required for interaction with coatomer' region

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

Similar variants

ARFGAP2 p.Ala227Thr Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala259Thr Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala266Val Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala272Thr Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala421Val Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala443Val Uncertain significance ★ ⚠ same type
ARFGAP2 p.Ala500Pro Uncertain significance ★ ⚠ same type
ARFGAP2 p.Arg119Trp Uncertain significance ★ ⚠ same type

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-glu289gly (accessed [today's date]).

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