TBCD p.Arg542=
c.1626A>G · rs374990865 · VCV2707426
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.06%, 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 0.63 | GERP -3.1, phastCons 0.007 |
| Overall | ||
| CADD | 4.715 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.06%
African / African-American · 45/75,020 alleles
Filtering AF
0.046%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0411%
Overall
0.00292%
47/1,610,420 alleles · ultra-rare
exomes 24/1,458,108 · genomes 23/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.06% | 1,667 |
| Middle Eastern | 0.0165% | 6,054 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,364 |
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
- TBCD
- Protein
- p.Arg542=
- Coding
- c.1626A>G
- MANE Select
- NM_005993
- dbSNP
- rs374990865
- Type
- single nucleotide variant
- Location
- chr17:82893609 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.45 · 6 PDB
Similar variants
- TBCD p.Arg542Thr Uncertain significance ★ ⚠ same residue
- TBCD c.1224-2A>G Pathogenic/Likely pathogenic ★★ same type
- TBCD c.2007-2A>G Likely pathogenic ★★ same type
- TBCD p.Ala475Thr Pathogenic/Likely pathogenic ★★ same type
- TBCD p.Ala554Val Pathogenic/Likely pathogenic ★★ same type
- TBCD p.Arg113Ter Pathogenic/Likely pathogenic ★★ same type
- TBCD p.Arg303Ter Pathogenic/Likely pathogenic ★★ same type
- TBCD p.Arg323Ter Pathogenic/Likely pathogenic ★★ 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/tbcd-p-arg542 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown