TLR2 p.Pro456=
c.1368C>A · rs751701671 · VCV3044153
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0791%, sas)
Conditions
1
TLR2-related disorder
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 -0.95 | GERP -3.9 |
| Overall | ||
| CADD | 3.463 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0791%
South Asian · 72/91,032 alleles
Filtering AF
0.0643%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.059%
Overall
0.00452%
73/1,613,954 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0791% | 1,264 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
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
- TLR2
- Protein
- p.Pro456=
- Coding
- c.1368C>A
- MANE Select
- NM_001318789
- dbSNP
- rs751701671
- Type
- single nucleotide variant
- Location
- chr4:153704275 (GRCh38)
- Gene constraint
- LOEUF 1.432 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.87 · 7 PDB
Disease context
TLR2-related disorder
Similar variants
- TLR2 p.Ala26Val Likely benign same condition
- TLR2 p.Ala400= Benign same condition
- TLR2 p.Asn729Ser Benign same condition
- TLR2 p.Leu563= Benign same condition
- TLR2 p.Leu81Pro Likely benign same condition
- TLR2 p.Phe707= Benign same condition
- TLR2 p.Thr411Ile Benign same condition
- TLR2 p.Thr65= Likely benign same condition
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/tlr2-p-pro456 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown