ARHGAP40 p.Pro25Ser
c.73C>T · rs767903943 · VCV2360685
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0641%, mid)
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 1.6 | GERP 1, phastCons 0.13 |
| Regional constraint | o/e 0.85 | unconstrained · MANE · 48 kb · p 1.3e-05 · regional, not allelic |
| Overall | ||
| CADD | 18.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0641%
Middle Eastern · 2/3,122 alleles
Filtering AF
0.0114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00469%
Overall
0.00155%
20/1,287,500 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0641% | 1,561 |
| South Asian | 0.00742% | 13,480 |
| Remaining individualsnot grpmax-eligible | 0.00691% | 14,474 |
| Admixed American | 0.0023% | 43,522 |
| African / African-American | 0.00152% | 65,786 |
| European (non-Finnish) | 0.000708% | 141,206 |
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
- ARHGAP40
- Protein
- p.Pro25Ser
- Coding
- c.73C>T
- MANE Select
- NM_001164431
- dbSNP
- rs767903943
- Type
- single nucleotide variant
- Location
- chr20:38602015 (GRCh38)
- Gene constraint
- LOEUF 0.718 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.96
Similar variants
- ARHGAP40 p.Ala153Val Uncertain significance ★ ⚠ same type
- ARHGAP40 p.Ala200Asp Uncertain significance ★ ⚠ same type
- ARHGAP40 p.Ala227Asp Uncertain significance ★ ⚠ same type
- ARHGAP40 p.Ala233Val Uncertain significance ★ ⚠ same type
- ARHGAP40 p.Ala296Val Uncertain significance ★ ⚠ same type
- ARHGAP40 p.Ala385Gly Uncertain significance ★ ⚠ same type
- ARHGAP40 p.Ala398Thr Uncertain significance ★ ⚠ same type
- ARHGAP40 p.Ala423Thr 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/arhgap40-p-pro25ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown