Is TICAM1 p.Pro110= (c.330C>T) pathogenic?

TICAM1 p.Pro110= (c.330C>T) is classified Likely benign in TICAM1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-08). Very rare (popmax 0.00881%, nfe); Associated with herpes simplex encephalitis, susceptibility to, 4.

What condition is associated with TICAM1 p.Pro110= (c.330C>T)?

TICAM1 p.Pro110= (c.330C>T) is associated with herpes simplex encephalitis, susceptibility to, 4 (ClinVar).

How common is TICAM1 p.Pro110= (c.330C>T) in the general population?

TICAM1 p.Pro110= (c.330C>T) is very rare (popmax 0.00881%, nfe) (gnomAD).

TICAM1 p.Pro110=

c.330C>T · rs373242041 · VCV473294

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00881%, nfe)

Conditions

herpes simplex encephalitis, susceptibility to, 4

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 -20	GERP -4.8
Overall
CADD	0.034	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00881% European (non-Finnish) · 104/1,179,926 alleles

Filtering AF 0.00741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00692%

Overall 0.00678% 109/1,608,456 alleles · very rare exomes 102/1,456,232 · genomes 7/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00881%	11,345
Remaining individualsnot grpmax-eligible	0.0032%	31,217
Admixed American	0.00167%	59,986
African / African-American	0.00133%	74,928
South Asian	0.0011%	91,088

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: TICAM1
Protein: p.Pro110=
Coding: c.330C>T
MANE Select: NM_182919
dbSNP: rs373242041
Type: single nucleotide variant
Location: chr19:4818048 (GRCh38)
Gene constraint: LOEUF 1.802 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 63.88 · 8 PDB
Residue 110: the 'trif-ntd' region

Full TICAM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

herpes simplex encephalitis, susceptibility to, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TICAM1 p.Ala111Thr Uncertain significance ★★ ⚠ same condition
TICAM1 p.Ala309Val Uncertain significance ★★ ⚠ same condition
TICAM1 p.Ala45Asp Uncertain significance ★★ ⚠ same condition
TICAM1 p.Ala45Val Uncertain significance ★★ ⚠ same condition
TICAM1 p.Ala684Thr Uncertain significance ★★ ⚠ same condition
TICAM1 p.Ala703Thr Uncertain significance ★★ ⚠ same condition
TICAM1 p.Arg132Gln Uncertain significance ★★ ⚠ same condition
TICAM1 p.Arg143Gln 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/ticam1-p-pro110 (accessed [today's date]).

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