USP25 p.Ala718=
c.2154G>A · VCV4872488
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.791%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.038 | phastCons 0.03 |
| Overall | ||
| CADD | 10.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.791%
African / African-American · 594/75,056 alleles
Filtering AF
0.739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.718%
Overall
0.0422%
681/1,614,044 alleles · rare
exomes 313/1,461,748 · genomes 368/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.791% | 126 |
| Admixed American | 0.0566% | 1,765 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,717 |
| East Asian | 0.00892% | 11,212 |
| South Asian | 0.00659% | 15,179 |
| European (non-Finnish) | 0.00161% | 62,103 |
| Finnishnot grpmax-eligible | 0.00156% | 64,008 |
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
- USP25
- Protein
- p.Ala718=
- Coding
- c.2154G>A
- MANE Select
- NM_001283041
- Type
- single nucleotide variant
- Location
- chr21:15833508 (GRCh38)
- Gene constraint
- LOEUF 0.635 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.12 · 7 PDB
Similar variants
- USP25 p.Ala718Val Uncertain significance ★ ⚠ same residue
- USP25 p.Arg217Gln Uncertain significance ★★ ⚠ same type
- USP25 p.Val596Ile Uncertain significance ★★ ⚠ same type
- USP25 p.Ala474Thr Uncertain significance ★ ⚠ same type
- USP25 p.Ala659Ser Uncertain significance ★ ⚠ same type
- USP25 p.Ala705Val Uncertain significance ★ ⚠ same type
- USP25 p.Ala919Thr Uncertain significance ★ ⚠ same type
- USP25 p.Arg1058Gln 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/usp25-p-ala718 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown