Is TRAF3 p.Asp324fs (c.969dup) pathogenic?

TRAF3 p.Asp324fs (c.969dup) is classified Uncertain significance in TRAF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). No gnomAD frequency available for this variant; Associated with herpes simplex encephalitis, susceptibility to, 3.

What condition is associated with TRAF3 p.Asp324fs (c.969dup)?

TRAF3 p.Asp324fs (c.969dup) is associated with herpes simplex encephalitis, susceptibility to, 3 (ClinVar).

How common is TRAF3 p.Asp324fs (c.969dup) in the general population?

TRAF3 p.Asp324fs (c.969dup) is no gnomAD frequency available for this variant (gnomAD).

TRAF3 p.Asp324fs

c.969dup · rs1890396534 · VCV1047312

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

herpes simplex encephalitis, susceptibility to, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 11 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.8	GERP 1.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TRAF3
Protein: p.Asp324fs
Coding: c.969dup
MANE Select: NM_145725
dbSNP: rs1890396534
Type: Duplication
Location: chr14:102903262 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.26 · 10 PDB
Residue 324: a UniProt-annotated variant site (in imd132b; likely pathogenic; decreased traf3 mrna and protein levels and absence of a truncated traf3 protein in patient cells)

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.Val476fs Uncertain significance ★ same condition
TRAF3 c.1135+4_1135+9dup Likely benign ★ same condition
TRAF3 c.297+19dup Benign ★ same condition
TRAF3 c.297+21dup Likely benign ★ same condition
TRAF3 c.402+20dup Likely benign ★ same condition
TRAF3 c.819+16dup Likely benign ★ same condition
TRAF3 p.Trp344Ter Pathogenic ★★ same condition
TRAF3 p.Ala188Val 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-asp324fs (accessed [today's date]).

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