TBL3 p.Ser418=
c.1254C>T · rs558798562 · VCV735152
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00364%, nfe)
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 -8.3 | GERP -2.8 |
| Overall | ||
| CADD | 2.183 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00364%
European (non-Finnish) · 43/1,180,000 alleles
Filtering AF
0.00275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00244%
Overall
0.00316%
51/1,613,908 alleles · very rare
exomes 47/1,461,664 · genomes 4/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00364% | 27,442 |
| Admixed American | 0.00333% | 29,999 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,236 |
| African / African-American | 0.00267% | 37,474 |
| South Asian | 0.0022% | 45,545 |
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
- TBL3
- Protein
- p.Ser418=
- Coding
- c.1254C>T
- MANE Select
- NM_006453
- dbSNP
- rs558798562
- Type
- single nucleotide variant
- Location
- chr16:1976276 (GRCh38)
- Gene constraint
- LOEUF 0.885 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.48 · 3 PDB
Similar variants
- TBL3 c.1742+8G>C Benign ★★ same type
- TBL3 p.Arg86= Benign ★★ same type
- NOXO1 c.223+1G>C Uncertain significance ★ ⚠ same type
- NOXO1 p.Ala278Val Uncertain significance ★ ⚠ same type
- NOXO1 p.Gly312Asp Uncertain significance ★ ⚠ same type
- TBL3 p.Ala106Thr Uncertain significance ★ ⚠ same type
- TBL3 p.Ala106Val Uncertain significance ★ same type
- TBL3 p.Ala158Gly 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/tbl3-p-ser418 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown