ARHGAP8 p.Ile374=
c.1122C>A · rs149982577 · VCV778958
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.969%, 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 -5.5 | GERP -2.3 |
| Overall | ||
| CADD | 0.036 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.969%
African / African-American · 727/75,016 alleles
Filtering AF
0.911%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.887%
Overall
0.0563%
909/1,614,070 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.969% | 103 |
| Middle Eastern | 0.198% | 505 |
| Remaining individualsnot grpmax-eligible | 0.102% | 977 |
| Admixed American | 0.0533% | 1,876 |
| South Asian | 0.00769% | 13,011 |
| European (non-Finnish) | 0.00559% | 17,879 |
| East Asian | 0.00223% | 44,864 |
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
- ARHGAP8
- Protein
- p.Ile374=
- Coding
- c.1122C>A
- MANE Select
- NM_181335
- dbSNP
- rs149982577
- Type
- single nucleotide variant
- Location
- chr22:44862415 (GRCh38)
- Gene constraint
- LOEUF 1.648 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.51
- Residue 374
- the rho-gap domain
Similar variants
- ARHGAP8 p.Ile374Met Uncertain significance ★ ⚠ same residue
- ARHGAP8 p.Pro176Leu Benign ★★ same type
- ARHGAP8 p.Ala235Thr Uncertain significance ★ ⚠ same type
- ARHGAP8 p.Ala362Thr Uncertain significance ★ ⚠ same type
- ARHGAP8 p.Ala386Val Uncertain significance ★ ⚠ same type
- ARHGAP8 p.Ala413Val Uncertain significance ★ ⚠ same type
- ARHGAP8 p.Arg162Gly Uncertain significance ★ ⚠ same type
- ARHGAP8 p.Arg185Gln 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/arhgap8-p-ile374 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown