ARHGAP45 p.Leu138=
c.412T>C · rs3764653 · VCV1262943
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 52%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.75 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -2.8 |
| Overall | ||
| CADD | 7.387 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
52%
African / African-American · 38,857/74,660 alleles
Filtering AF
51.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 51.4%
Overall
37.2%
598,453/1,610,260 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 52% | 2 |
| Admixed American | 41.9% | 2 |
| South Asian | 38.5% | 3 |
| Remaining individualsnot grpmax-eligible | 37% | 3 |
| Finnishnot grpmax-eligible | 36.2% | 3 |
| European (non-Finnish) | 36.2% | 3 |
| East Asian | 35.5% | 3 |
| Middle Eastern | 33.9% | 3 |
| Amishnot grpmax-eligible | 31.6% | 3 |
| Ashkenazi Jewishnot grpmax-eligible | 31.5% | 3 |
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
- ARHGAP45
- Protein
- p.Leu138=
- Coding
- c.412T>C
- MANE Select
- NM_012292
- dbSNP
- rs3764653
- Type
- single nucleotide variant
- Location
- chr19:1068735 (GRCh38)
- Gene constraint
- LOEUF 0.75 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 67.96 · 2 PDB
Similar variants
- ARHGAP45 c.422-1836C>T Benign ★★ same type
- ARHGAP45 p.Ala426Val Benign ★★ ⚠ same type
- ARHGAP45 p.Arg139His Benign ★★ same type
- ARHGAP45 p.Glu1090Gly Benign ★★ same type
- ARHGAP45 p.Gly1019Arg Likely benign ★★ same type
- ARHGAP45 p.Pro1011= Benign ★★ same type
- ARHGAP45 p.Ser1032= Benign ★★ same type
- ARHGAP45 p.Val805= Benign ★★ 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/arhgap45-p-leu138 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown