Is ARFGAP2 p.Ala500Pro (c.1498G>C) pathogenic?

ARFGAP2 p.Ala500Pro (c.1498G>C) is classified Uncertain significance in ARFGAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). AlphaMissense: likely pathogenic (0.999); Absent from gnomAD v4.1.

How common is ARFGAP2 p.Ala500Pro (c.1498G>C) in the general population?

ARFGAP2 p.Ala500Pro (c.1498G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARFGAP2 p.Ala500Pro (c.1498G>C)?

AlphaMissense predicts likely pathogenic (score 0.999) — an in-silico prediction, not a clinical call.

ARFGAP2 p.Ala500Pro

c.1498G>C · VCV3888376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.999	likely pathogenic · top 3% in ARFGAP2
REVEL	0.687	pathogenic-leaning
SaProt	LLR -11.61	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.12 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Ala500Pro
Coding: c.1498G>C
MANE Select: NM_032389
Type: single nucleotide variant
Location: chr11:47166315 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.19 · 1 PDB
Residue 500: 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.Arg119Trp Uncertain significance ★ ⚠ same type
ARFGAP2 p.Arg255Gly 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-ala500pro (accessed [today's date]).

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