Is ARFGEF2 p.Arg13= (c.39G>A) pathogenic?

ARFGEF2 p.Arg13= (c.39G>A) is classified Likely benign in ARFGEF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). Very rare (popmax 0.00194%, amr).

How common is ARFGEF2 p.Arg13= (c.39G>A) in the general population?

ARFGEF2 p.Arg13= (c.39G>A) is very rare (popmax 0.00194%, amr) (gnomAD).

ARFGEF2 p.Arg13=

c.39G>A · rs930880468 · VCV1947448

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00194%, amr)

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 5.5	GERP -0.37, phastCons 1
Overall
CADD	14.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00194% Admixed American · 1/51,546 alleles

Filtering AF 0.000556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000439%

Overall 0.000898% 14/1,558,178 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00194%	51,546
Remaining individualsnot grpmax-eligible	0.00166%	60,354
European (non-Finnish)	0.00104%	95,929

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: ARFGEF2
Protein: p.Arg13=
Coding: c.39G>A
MANE Select: NM_006420
dbSNP: rs930880468
Type: single nucleotide variant
Location: chr20:48921928 (GRCh38)
Gene constraint: LOEUF 0.391 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.59 · 2 PDB
Residue 13: the 'dcb; dcb:dcb domain and dcb:hus domain interaction' region

Full ARFGEF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARFGEF2 c.4315+5T>G Uncertain significance ★★ same type
ARFGEF2 c.4316-12T>C Uncertain significance ★★ same type
ARFGEF2 c.*368A>G Uncertain significance ★★ same type
ARFGEF2 p.Ala270Thr Uncertain significance ★★ ⚠ same type
ARFGEF2 p.Ala701Thr Uncertain significance ★★ ⚠ same type
ARFGEF2 p.Arg1012Cys Uncertain significance ★★ ⚠ same type
ARFGEF2 p.Arg1012His Uncertain significance ★★ ⚠ same type
ARFGEF2 p.Arg1019His 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/arfgef2-p-arg13 (accessed [today's date]).

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