ARHGEF18 p.Ala487Ser
c.1459G>T · VCV4940292
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.111 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.7 | GERP 0.71, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 107 kb · p 1.6e-07 · regional, not allelic |
| Overall | ||
| CADD | 11.08 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,940 alleles
Overall
6.2e-05%
1/1,613,550 alleles · very rare
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
- ARHGEF18
- Protein
- p.Ala487Ser
- Coding
- c.1459G>T
- MANE Select
- NM_001367823
- Type
- single nucleotide variant
- Location
- chr19:7444302 (GRCh38)
- Gene constraint
- LOEUF 0.811 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.10
- Residue 487
- the dh domain
Similar variants
- ARHGEF18 p.Ala487= Likely benign ★ same residue
- ARHGEF18 c.2905-1G>T Likely pathogenic ★★ same type
- ARHGEF18 p.Arg943Ter Pathogenic/Likely pathogenic ★★ same type
- ARHGEF18 c.1107-3C>G Uncertain significance ★★ same type
- ARHGEF18 c.2904+5G>A Uncertain significance ★★ same type
- ARHGEF18 c.968-127A>G Uncertain significance ★★ same type
- ARHGEF18 c.968-19G>T Uncertain significance ★★ same type
- ARHGEF18 c.968-24A>G 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/arhgef18-p-ala487ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown