TUBA8 p.Asp33=
c.99C>T · rs141954140 · VCV1622691
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, afr)
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 -2.8 | |
| Overall | ||
| CADD | 12.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
African / African-American · 20/74,936 alleles
Filtering AF
0.0177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.00353%
57/1,614,106 alleles · ultra-rare
exomes 46/1,461,886 · genomes 11/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0267% | 3,747 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,415 |
| Finnishnot grpmax-eligible | 0.00625% | 16,011 |
| East Asian | 0.00445% | 22,448 |
| Admixed American | 0.00333% | 30,003 |
| South Asian | 0.00329% | 30,363 |
| European (non-Finnish) | 0.00161% | 62,108 |
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
- TUBA8
- Protein
- p.Asp33=
- Coding
- c.99C>T
- MANE Select
- NM_018943
- dbSNP
- rs141954140
- Type
- single nucleotide variant
- Location
- chr22:18121574 (GRCh38)
- Gene constraint
- LOEUF 1.117 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.24
Similar variants
- TUBA8 p.Ala273Thr Uncertain significance ★★ ⚠ same type
- TUBA8 p.Ala383Val Uncertain significance ★★ ⚠ same type
- TUBA8 p.Ala385Glu Uncertain significance ★★ ⚠ same type
- TUBA8 p.Ala385Val Uncertain significance ★★ same type
- TUBA8 p.Ala400Thr Uncertain significance ★★ ⚠ same type
- TUBA8 p.Arg121Cys Uncertain significance ★★ ⚠ same type
- TUBA8 p.Arg121His Uncertain significance ★★ ⚠ same type
- TUBA8 p.Arg156Cys 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/tuba8-p-asp33 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown