TUBA8 p.Pro63=
c.189C>T · rs199826214 · VCV1609249
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.067%, sas)
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 -0.21 | phastCons 0.082 |
| Overall | ||
| CADD | 13.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.067%
South Asian · 61/91,096 alleles
Filtering AF
0.0535%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0486%
Overall
0.012%
193/1,614,082 alleles · ultra-rare
exomes 182/1,461,886 · genomes 11/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.067% | 1,493 |
| Middle Eastern | 0.0329% | 3,042 |
| European (non-Finnish) | 0.0103% | 9,672 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,414 |
| Admixed American | 0.00167% | 59,996 |
| African / African-American | 0.00133% | 74,924 |
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.Pro63=
- Coding
- c.189C>T
- MANE Select
- NM_018943
- dbSNP
- rs199826214
- Type
- single nucleotide variant
- Location
- chr22:18121664 (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-pro63 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown