STUB1 p.Arg66=
c.198G>A · VCV3674150
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00176%, amr)
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 · G>T here scores Δ0.26 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.8 | GERP -4.1, phastCons 1 |
| Overall | ||
| CADD | 11.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00176%
Admixed American · 1/56,832 alleles
Filtering AF
0.000125%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9.1e-05%
Overall
0.000416%
6/1,442,122 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00176% | 56,832 |
| European (non-Finnish) | 0.000427% | 234,275 |
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
- STUB1
- Protein
- p.Arg66=
- Coding
- c.198G>A
- MANE Select
- NM_005861
- Type
- single nucleotide variant
- Location
- chr16:681190 (GRCh38)
- Gene constraint
- LOEUF 1.294 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 89.84 · 27 PDB
- Residue 66
- an α-helix
Similar variants
- STUB1 p.Arg66Gln Uncertain significance ★ ⚠ same residue
- STUB1 p.Arg66Trp Uncertain significance ★ same residue
- STUB1 p.Asn65Ser Pathogenic/Likely pathogenic ★★ same type
- STUB1 p.Tyr49Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- STUB1 p.Ala11Thr Uncertain significance ★★ ⚠ same type
- STUB1 p.Arg173Leu Uncertain significance ★★ ⚠ same type
- STUB1 p.Arg35Pro Uncertain significance ★★ ⚠ same type
- STUB1 p.Asn34Ser 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/stub1-p-arg66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown