TLR4 p.Ser545=
c.1635C>T · rs140976297 · VCV766142
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00102%, 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 -1.6 | GERP -3.8 |
| Overall | ||
| CADD | 0.457 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00102%
European (non-Finnish) · 12/1,180,018 alleles
Filtering AF
0.000542%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000428%
Overall
0.000744%
12/1,613,814 alleles · very rare
exomes 9/1,461,676 · genomes 3/152,138 · joint denominator
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
- TLR4
- Protein
- p.Ser545=
- Coding
- c.1635C>T
- MANE Select
- NM_138554
- dbSNP
- rs140976297
- Type
- single nucleotide variant
- Location
- chr9:117713763 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.42 · 15 PDB
Similar variants
- TLR4 c.*2010G>C Benign ★★ same type
- TLR4 p.Gln163= Benign ★★ same type
- TLR4 p.Lys354= Benign/Likely benign ★★ same type
- TLR4 p.Lys653= Benign ★★ same type
- TLR4 p.Phe443= Likely benign ★★ same type
- TLR4 p.Pro113= Benign/Likely benign ★★ same type
- TLR4 p.Pro145= Benign/Likely benign ★★ same type
- TLR4 c.*4092C>T 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/tlr4-p-ser545 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown