Is TRAF3 p.Pro18= (c.54G>A) pathogenic?

TRAF3 p.Pro18= (c.54G>A) is classified Likely benign in TRAF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). Very rare (popmax 0.00223%, eas); Associated with herpes simplex encephalitis, susceptibility to, 3.

What condition is associated with TRAF3 p.Pro18= (c.54G>A)?

TRAF3 p.Pro18= (c.54G>A) is associated with herpes simplex encephalitis, susceptibility to, 3 (ClinVar).

How common is TRAF3 p.Pro18= (c.54G>A) in the general population?

TRAF3 p.Pro18= (c.54G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

TRAF3 p.Pro18=

c.54G>A · rs775197332 · VCV2055042

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

herpes simplex encephalitis, susceptibility to, 3

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 -4.1	GERP -3.9
Overall
CADD	1.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000496% 8/1,614,018 alleles · very rare exomes 6/1,461,880 · genomes 2/152,138 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
Admixed American	0.00167%	60,008
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000424%	236,004

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: TRAF3
Protein: p.Pro18=
Coding: c.54G>A
MANE Select: NM_145725
dbSNP: rs775197332
Type: single nucleotide variant
Location: chr14:102870255 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.26 · 10 PDB
Residue 18: the 'disordered' region

Full TRAF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

herpes simplex encephalitis, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TRAF3 p.Pro18Leu Uncertain significance ★★ ⚠ same residue
TRAF3 p.Pro18Arg Uncertain significance ⚠ same residue
TRAF3 p.Trp344Ter Pathogenic ★★ same condition
TRAF3 p.Ala188Val Uncertain significance ★★ ⚠ same condition
TRAF3 p.Ala371Thr Uncertain significance ★★ ⚠ same condition
TRAF3 p.Ala371Val Uncertain significance ★★ ⚠ same condition
TRAF3 p.Ala78Val Uncertain significance ★★ ⚠ same condition
TRAF3 p.Ala90Val 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/traf3-p-pro18 (accessed [today's date]).

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