ARHGAP25 p.Val558Ala
c.1673T>C · VCV3422322
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.122 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.1 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 91 kb · p 0.00048 · regional, not allelic |
| Overall | ||
| CADD | 18.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,050 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000248%
4/1,613,748 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,525 |
| African / African-American | 0.00134% | 74,868 |
| European (non-Finnish) | 8.47e-05% | 1,179,984 |
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.Val558Ala
- Coding
- c.1673T>C
- MANE Select
- NM_001007231
- Type
- single nucleotide variant
- Location
- chr2:68822812 (GRCh38)
- Gene constraint
- LOEUF 0.627 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.41 · 1 PDB
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-val558ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown