Is TICAM1 p.Pro643= (c.1929G>A) pathogenic?

TICAM1 p.Pro643= (c.1929G>A) is classified Benign/Likely benign in TICAM1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-17). Rare (popmax 0.512%, eas); Associated with herpes simplex encephalitis, susceptibility to, 4.

What condition is associated with TICAM1 p.Pro643= (c.1929G>A)?

TICAM1 p.Pro643= (c.1929G>A) is associated with herpes simplex encephalitis, susceptibility to, 4 (ClinVar).

How common is TICAM1 p.Pro643= (c.1929G>A) in the general population?

TICAM1 p.Pro643= (c.1929G>A) is rare (popmax 0.512%, eas) (gnomAD).

TICAM1 p.Pro643=

c.1929G>A · rs201978370 · VCV1164830

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.512%, eas)

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 -12	GERP -2
Overall
CADD	0.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.512% East Asian · 117/22,872 alleles

Filtering AF 0.436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.408%

Overall 0.0111% 145/1,303,114 alleles · rare exomes 124/1,170,946 · genomes 21/132,168 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.512%	195
South Asian	0.023%	4,344
Remaining individualsnot grpmax-eligible	0.0135%	7,390
Finnishnot grpmax-eligible	0.0027%	37,024
African / African-American	0.00166%	60,268
European (non-Finnish)	0.000201%	498,512

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.Pro643=
Coding: c.1929G>A
MANE Select: NM_182919
dbSNP: rs201978370
Type: single nucleotide variant
Location: chr19:4816449 (GRCh38)
Gene constraint: LOEUF 1.802 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 63.88 · 8 PDB
Residue 643: the 'sufficient to induce apoptosis' region; the 'disordered' 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.Pro643Arg Uncertain significance ★ ⚠ same residue
TICAM1 p.Pro643Ser Uncertain significance ★ ⚠ same residue
TICAM1 p.Pro643fs Uncertain significance ★ same residue
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

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-pro643 (accessed [today's date]).

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