ARHGAP12 p.Pro590=
c.1770G>A · VCV4281019
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.744%, afr)
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 -1.2 | GERP -3.5, phastCons 0.002 |
| Overall | ||
| CADD | 10.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.744%
African / African-American · 558/75,030 alleles
Filtering AF
0.693%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.672%
Overall
0.0392%
633/1,613,988 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.744% | 134 |
| Remaining individualsnot grpmax-eligible | 0.0528% | 1,894 |
| Admixed American | 0.03% | 3,334 |
| South Asian | 0.00329% | 30,355 |
| European (non-Finnish) | 0.00178% | 56,188 |
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
- ARHGAP12
- Protein
- p.Pro590=
- Coding
- c.1770G>A
- MANE Select
- NM_018287
- Type
- single nucleotide variant
- Location
- chr10:31814323 (GRCh38)
- Gene constraint
- LOEUF 0.681 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.68
- Residue 590
- the 'disordered' region
Similar variants
- ARHGAP12 p.Arg6= Benign ★★ same type
- ARHGAP12 p.Ala393Val Uncertain significance ★ ⚠ same type
- ARHGAP12 p.Ala458Ser Uncertain significance ★ ⚠ same type
- ARHGAP12 p.Ala458Val Uncertain significance ★ ⚠ same type
- ARHGAP12 p.Ala491Ser Uncertain significance ★ ⚠ same type
- ARHGAP12 p.Ala491Val Uncertain significance ★ ⚠ same type
- ARHGAP12 p.Ala698Thr Uncertain significance ★ ⚠ same type
- ARHGAP12 p.Ala753Ser 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/arhgap12-p-pro590 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown