TBC1D2B p.Pro336=
c.1008G>A · VCV3770670
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.108%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.003 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.2 |
| Overall | ||
| CADD | 0.445 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.108%
Admixed American · 65/60,020 alleles
Filtering AF
0.0871%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0795%
Overall
0.0606%
978/1,613,884 alleles · rare
exomes 902/1,461,652 · genomes 76/152,232 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.108% | 923 |
| European (non-Finnish) | 0.0722% | 1,385 |
| Remaining individualsnot grpmax-eligible | 0.0624% | 1,602 |
| Middle Eastern | 0.0332% | 3,009 |
| African / African-American | 0.0187% | 5,358 |
| South Asian | 0.00549% | 18,214 |
| East Asian | 0.00223% | 44,884 |
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
- TBC1D2B
- Protein
- p.Pro336=
- Coding
- c.1008G>A
- MANE Select
- NM_144572
- Type
- single nucleotide variant
- Location
- chr15:78025337 (GRCh38)
- Gene constraint
- LOEUF 0.739 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.68
- Residue 336
- a UniProt-annotated variant site (in nedsgo; pathogenic); the 'disordered' region
Similar variants
- TBC1D2B p.Pro336Leu Uncertain significance ★ ⚠ same residue
- TBC1D2B p.Arg918Trp Uncertain significance ★★ ⚠ same type
- TBC1D2B p.Tyr66Cys Uncertain significance ★★ ⚠ same type
- TBC1D2B c.848-5T>C Benign/Likely benign ★★ same type
- TBC1D2B p.Gln819Arg Likely benign ★★ same type
- TBC1D2B p.Glu201Ter Likely pathogenic ★ same type
- TBC1D2B p.Trp672Ter Likely pathogenic ★ same type
- TBC1D2B c.1582-19A>G 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/tbc1d2b-p-pro336 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown