ARHGAP25 p.Ala417=
c.1251G>A · rs143476860 · VCV720550
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.31%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.043 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.16 | GERP -3.8 |
| Overall | ||
| CADD | 4.757 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.31%
African / African-American · 982/75,002 alleles
Filtering AF
1.24%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.21%
Overall
0.0696%
1,124/1,614,150 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.31% | 76 |
| Admixed American | 0.112% | 896 |
| Remaining individualsnot grpmax-eligible | 0.0864% | 1,158 |
| South Asian | 0.00659% | 15,181 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
| European (non-Finnish) | 0.00119% | 84,287 |
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
- ARHGAP25
- Protein
- p.Ala417=
- Coding
- c.1251G>A
- MANE Select
- NM_001007231
- dbSNP
- rs143476860
- Type
- single nucleotide variant
- Location
- chr2:68822390 (GRCh38)
- Gene constraint
- LOEUF 0.627 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.41 · 1 PDB
- Residue 417
- the 'disordered' region
Similar variants
- ARHGAP25 p.Ala101Thr Uncertain significance ★ same type
- ARHGAP25 p.Ala265Val Uncertain significance ★ same type
- ARHGAP25 p.Ala33Thr Uncertain significance ★ same type
- ARHGAP25 p.Ala34Thr Uncertain significance ★ same type
- ARHGAP25 p.Ala374Thr Uncertain significance ★ same type
- ARHGAP25 p.Ala517Thr Uncertain significance ★ same type
- ARHGAP25 p.Arg161His Uncertain significance ★ same type
- ARHGAP25 p.Arg193Gln 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/arhgap25-p-ala417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown