ARHGAP25 p.Met90Val
c.268A>G · VCV3311330
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.13 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -4.1, phastCons 0.47 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 91 kb · p 0.00048 · regional, not allelic |
| Overall | ||
| CADD | 8.568 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,058 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000274%
4/1,461,770 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,058 |
| European (non-Finnish) | 0.000254% | 393,320 |
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.Met90Val
- Coding
- c.268A>G
- MANE Select
- NM_001007231
- Type
- single nucleotide variant
- Location
- chr2:68782239 (GRCh38)
- Gene constraint
- LOEUF 0.627 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.41 · 1 PDB
- Residue 90
- the ph domain; a β-strand
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-met90val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown