TBC1D32 p.Pro342=
c.1026G>C · rs374800522 · VCV1905840
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.05%, mid)
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 -8.9 | GERP -3.8 |
| Overall | ||
| CADD | 0.073 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.05%
Middle Eastern · 3/6,000 alleles
Filtering AF
0.0142%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0113%
Overall
0.0047%
75/1,596,732 alleles · ultra-rare
exomes 69/1,444,672 · genomes 6/152,060 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.05% | 2,000 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0345% | 2,897 |
| Admixed American | 0.0235% | 4,261 |
| Remaining individualsnot grpmax-eligible | 0.00975% | 10,260 |
| European (non-Finnish) | 0.00351% | 28,502 |
| African / African-American | 0.00134% | 74,674 |
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
- TBC1D32
- Protein
- p.Pro342=
- Coding
- c.1026G>C
- MANE Select
- NM_152730
- dbSNP
- rs374800522
- Type
- single nucleotide variant
- Location
- chr6:121303671 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84
Similar variants
- TBC1D32 p.Pro342Leu Uncertain significance ★ ⚠ same residue
- TBC1D32 p.Arg734Ter Pathogenic/Likely pathogenic ★★ same type
- TBC1D32 p.Arg1104Thr Uncertain significance ★★ ⚠ same type
- TBC1D32 p.Arg135Gln Uncertain significance ★★ ⚠ same type
- TBC1D32 p.Arg287Cys Uncertain significance ★★ ⚠ same type
- TBC1D32 p.Arg287His Uncertain significance ★★ ⚠ same type
- TBC1D32 p.Arg820Cys Uncertain significance ★★ ⚠ same type
- TBC1D32 p.Arg884Trp 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/tbc1d32-p-pro342 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown