ARHGEF17 p.Pro8=
c.24C>G · rs376619433 · VCV2642134
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.333%, mid)
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 0.45 | GERP -1.3, phastCons 0.99 |
| Overall | ||
| CADD | 10.23 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.333%
Middle Eastern · 17/5,104 alleles
Filtering AF
0.212%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.174%
Overall
0.101%
1,526/1,513,106 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.333% | 300 |
| Ashkenazi Jewishnot grpmax-eligible | 0.268% | 373 |
| Amishnot grpmax-eligible | 0.219% | 456 |
| South Asian | 0.166% | 604 |
| Admixed American | 0.125% | 802 |
| Remaining individualsnot grpmax-eligible | 0.118% | 845 |
| European (non-Finnish) | 0.102% | 979 |
| African / African-American | 0.0145% | 6,906 |
| Finnishnot grpmax-eligible | 0.00549% | 18,223 |
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
- ARHGEF17
- Protein
- p.Pro8=
- Coding
- c.24C>G
- MANE Select
- NM_014786
- dbSNP
- rs376619433
- Type
- single nucleotide variant
- Location
- chr11:73308662 (GRCh38)
- Gene constraint
- LOEUF 0.57 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 51.50
Similar variants
- ARHGEF17 p.Asp1593= Benign ★★ same type
- ARHGEF17 p.Ser239Tyr Benign ★★ ⚠ same type
- ARHGEF17 p.Ala1049Thr Uncertain significance ★ ⚠ same type
- ARHGEF17 p.Ala111Val Uncertain significance ★ ⚠ same type
- ARHGEF17 p.Ala114Glu Uncertain significance ★ ⚠ same type
- ARHGEF17 p.Ala114Ser Uncertain significance ★ ⚠ same type
- ARHGEF17 p.Ala1240Val Uncertain significance ★ ⚠ same type
- ARHGEF17 p.Ala1261Val 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/arhgef17-p-pro8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown