Is TICAM1 p.Pro321= (c.963G>A) pathogenic?

TICAM1 p.Pro321= (c.963G>A) is classified Likely benign in TICAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). Very rare (popmax 0.00364%, nfe); Associated with herpes simplex encephalitis, susceptibility to, 4.

What condition is associated with TICAM1 p.Pro321= (c.963G>A)?

TICAM1 p.Pro321= (c.963G>A) is associated with herpes simplex encephalitis, susceptibility to, 4 (ClinVar).

How common is TICAM1 p.Pro321= (c.963G>A) in the general population?

TICAM1 p.Pro321= (c.963G>A) is very rare (popmax 0.00364%, nfe) (gnomAD).

TICAM1 p.Pro321=

c.963G>A · rs748972207 · VCV2885733

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00364%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.9	GERP -2.9
Overall
CADD	4.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00364% European (non-Finnish) · 43/1,180,022 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00297% 48/1,613,880 alleles · very rare exomes 47/1,461,822 · genomes 1/152,058 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,442
African / African-American	0.00267%	37,441
Admixed American	0.00167%	59,966
Remaining individualsnot grpmax-eligible	0.0016%	62,484
South Asian	0.0011%	91,084

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.Pro321=
Coding: c.963G>A
MANE Select: NM_182919
dbSNP: rs748972207
Type: single nucleotide variant
Location: chr19:4817415 (GRCh38)
Gene constraint: LOEUF 1.802 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 63.88 · 8 PDB

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-pro321 (accessed [today's date]).

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