USB1 p.Val71=
c.213G>A · rs369515724 · VCV769901
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.055%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.57 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.40 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -3.3 |
| Overall | ||
| CADD | 15.75 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.055%
Admixed American · 33/60,008 alleles
Filtering AF
0.0402%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0351%
Overall
0.00582%
94/1,613,938 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.055% | 1,818 |
| East Asian | 0.0111% | 8,978 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| European (non-Finnish) | 0.00441% | 22,693 |
| Finnishnot grpmax-eligible | 0.00156% | 63,918 |
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
- USB1
- Protein
- p.Val71=
- Coding
- c.213G>A
- MANE Select
- NM_024598
- dbSNP
- rs369515724
- Type
- single nucleotide variant
- Location
- chr16:58002593 (GRCh38)
- Gene constraint
- LOEUF 1.016 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 83.91 · 5 PDB
- Residue 71
- the 'disordered' region
Similar variants
- USB1 p.Val71Met Uncertain significance ★★ ⚠ same residue
- USB1 c.266-1G>A Pathogenic ★★ same type
- USB1 p.His208Arg Likely pathogenic ★★ same type
- USB1 p.Ala106Ser Uncertain significance ★★ ⚠ same type
- USB1 p.Ala218Thr Uncertain significance ★★ ⚠ same type
- USB1 p.Ala218Val Uncertain significance ★★ ⚠ same type
- USB1 p.Arg112Gln Uncertain significance ★★ ⚠ same type
- USB1 p.Arg112Trp 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/usb1-p-val71 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown