Is TLR3 p.Val55= (c.165G>C) pathogenic?

TLR3 p.Val55= (c.165G>C) is classified Likely benign in TLR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). Very rare (popmax 0.00667%, amr); Associated with herpes simplex encephalitis, susceptibility to, 1.

What condition is associated with TLR3 p.Val55= (c.165G>C)?

TLR3 p.Val55= (c.165G>C) is associated with herpes simplex encephalitis, susceptibility to, 1 (ClinVar).

How common is TLR3 p.Val55= (c.165G>C) in the general population?

TLR3 p.Val55= (c.165G>C) is very rare (popmax 0.00667%, amr) (gnomAD).

TLR3 p.Val55=

c.165G>C · rs139854420 · VCV1099990

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Conditions

herpes simplex encephalitis, susceptibility to, 1

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 0.51	GERP -1.5, phastCons 0.031
Overall
CADD	5.173	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/59,990 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00031% 5/1,614,016 alleles · very rare exomes 3/1,461,894 · genomes 2/152,122 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,997
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: TLR3
Protein: p.Val55=
Coding: c.165G>C
MANE Select: NM_003265
dbSNP: rs139854420
Type: single nucleotide variant
Location: chr4:186076784 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.64 · 20 PDB
Residue 55: a β-strand

Full TLR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

herpes simplex encephalitis, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TLR3 p.Ala185Val Uncertain significance ★★ ⚠ same condition
TLR3 p.Ala549Thr Uncertain significance ★★ ⚠ same condition
TLR3 p.Ala795Val Uncertain significance ★★ ⚠ same condition
TLR3 p.Ala839Asp Uncertain significance ★★ ⚠ same condition
TLR3 p.Arg331Gln Uncertain significance ★★ ⚠ same condition
TLR3 p.Arg331Trp Uncertain significance ★★ ⚠ same condition
TLR3 p.Arg809Lys Uncertain significance ★★ ⚠ same condition
TLR3 p.Arg885Gln Uncertain significance ★★ ⚠ 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/tlr3-p-val55 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown