Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.265%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.4 | GERP -1.5 |
| Overall | ||
| CADD | 5.559 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.265%
European (non-Finnish) · 3,127/1,180,010 alleles
Filtering AF
0.257%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.254%
Overall
0.221%
3,560/1,614,076 alleles · rare
exomes 3,344/1,461,762 · genomes 216/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.265% | 377 |
| Finnishnot grpmax-eligible | 0.22% | 454 |
| Remaining individualsnot grpmax-eligible | 0.149% | 672 |
| South Asian | 0.124% | 806 |
| Admixed American | 0.06% | 1,667 |
| Middle Eastern | 0.0495% | 2,020 |
| African / African-American | 0.048% | 2,085 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0372% | 2,691 |
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.Phe443=
- Coding
- c.1329C>T
- MANE Select
- NM_138554
- dbSNP
- rs5030716
- Type
- single nucleotide variant
- Location
- chr9:117713457 (GRCh38)
- Gene constraint
- LOEUF 0.858 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.42 · 15 PDB
- Residue 443
- a turn; a UniProt-annotated variant site (in)
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.Pro113= Benign/Likely benign ★★ same type
- TLR4 p.Pro145= Benign/Likely benign ★★ same type
- TLR4 c.*4092C>T Uncertain significance ★ same type
- TLR4 p.Ala121Ser 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-phe443 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown