ARFGEF2 p.Pro27=
c.81C>G · rs368957600 · VCV707703
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.334%, eas)
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 1.3 | GERP 0.7, phastCons 1 |
| Overall | ||
| CADD | 13.82 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.334%
East Asian · 143/42,866 alleles
Filtering AF
0.289%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.272%
Overall
0.0122%
192/1,577,208 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.334% | 300 |
| Remaining individualsnot grpmax-eligible | 0.0737% | 1,357 |
| Admixed American | 0.00184% | 54,320 |
| South Asian | 0.00116% | 86,034 |
| European (non-Finnish) | 0.000172% | 580,892 |
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.Pro27=
- Coding
- c.81C>G
- MANE Select
- NM_006420
- dbSNP
- rs368957600
- Type
- single nucleotide variant
- Location
- chr20:48921970 (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 27
- the 'dcb; dcb:dcb domain and dcb:hus domain interaction' region
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-pro27 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown