Is ARFGAP2 p.Gly519Ser (c.1555G>A) pathogenic?

ARFGAP2 p.Gly519Ser (c.1555G>A) is classified Likely benign in ARFGAP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-23). AlphaMissense: likely benign (0.1806); Rare (popmax 0.672%, nfe); Associated with ARFGAP2-related disorder.

What condition is associated with ARFGAP2 p.Gly519Ser (c.1555G>A)?

ARFGAP2 p.Gly519Ser (c.1555G>A) is associated with ARFGAP2-related disorder (ClinVar).

How common is ARFGAP2 p.Gly519Ser (c.1555G>A) in the general population?

ARFGAP2 p.Gly519Ser (c.1555G>A) is rare (popmax 0.672%, nfe) (gnomAD).

What do computational predictors say about ARFGAP2 p.Gly519Ser (c.1555G>A)?

AlphaMissense predicts likely benign (score 0.1806) — an in-silico prediction, not a clinical call.

ARFGAP2 p.Gly519Ser

c.1555G>A · rs142683966 · VCV3044117

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1806 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.672%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARFGAP2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1806	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.4, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 11 kb · p 0.12 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.672% European (non-Finnish) · 7,784/1,158,064 alleles

Filtering AF 0.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.655%

Overall 0.54% 8,476/1,569,028 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.672%	149
Remaining individualsnot grpmax-eligible	0.516%	194
Admixed American	0.343%	292
Finnishnot grpmax-eligible	0.148%	678
African / African-American	0.108%	927
South Asian	0.0235%	4,262
Middle Eastern	0.0171%	5,862
Ashkenazi Jewishnot grpmax-eligible	0.0106%	9,476
East Asian	0.00712%	14,043

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.Gly519Ser
Coding: c.1555G>A
MANE Select: NM_032389
dbSNP: rs142683966
Type: single nucleotide variant
Location: chr11:47165493 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.19 · 1 PDB
Residue 519: 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 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.Ala266= 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-gly519ser (accessed [today's date]).

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