Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 8.78%, afr) — too common for a highly-penetrant pathogenic allele
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 -5.7 | GERP -5.5 |
| Overall | ||
| CADD | 0.325 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.78%
African / African-American · 6,589/75,026 alleles
Filtering AF
8.61%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.53%
Overall
0.475%
7,669/1,613,776 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.78% | 11 |
| Admixed American | 0.738% | 135 |
| Remaining individualsnot grpmax-eligible | 0.669% | 149 |
| Middle Eastern | 0.478% | 209 |
| South Asian | 0.0395% | 2,530 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0135% | 7,401 |
| European (non-Finnish) | 0.0127% | 7,865 |
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
- ARHGAP35
- Protein
- p.Pro581=
- Coding
- c.1743G>A
- MANE Select
- NM_004491
- dbSNP
- rs7250030
- Type
- single nucleotide variant
- Location
- chr19:46920418 (GRCh38)
- Gene constraint
- LOEUF 0.204 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.08 · 6 PDB
Similar variants
- ARHGAP35 p.Pro581Leu Uncertain significance ★ ⚠ same residue
- ARHGAP35 p.Arg1164= Benign ★★ same type
- ARHGAP35 p.Leu125= Benign ★★ same type
- ARHGAP35 p.Arg109Ter Likely pathogenic ★ same type
- ARHGAP35 p.Gln1067Ter Pathogenic ★ same type
- ARHGAP35 p.Gln1352Ter Pathogenic ★ same type
- ARHGAP35 p.Gln534Ter Likely pathogenic ★ same type
- ARHGAP35 p.Lys118Ter Likely pathogenic ★ 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/arhgap35-p-pro581 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown