Is TRAF3 p.Ser370= (c.1110C>T) pathogenic?

TRAF3 p.Ser370= (c.1110C>T) is classified Benign in TRAF3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.39%, afr); Associated with herpes simplex encephalitis, susceptibility to, 3.

What condition is associated with TRAF3 p.Ser370= (c.1110C>T)?

TRAF3 p.Ser370= (c.1110C>T) is associated with herpes simplex encephalitis, susceptibility to, 3 (ClinVar).

How common is TRAF3 p.Ser370= (c.1110C>T) in the general population?

TRAF3 p.Ser370= (c.1110C>T) is low-frequency (popmax 2.39%, afr) (gnomAD).

TRAF3 p.Ser370=

c.1110C>T · rs1051743 · VCV473287

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.39%, afr)

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 -8.8	GERP -2.6
Overall
CADD	1.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.39% African / African-American · 1,795/74,988 alleles

Filtering AF 2.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.26%

Overall 0.158% 2,554/1,613,988 alleles · low-frequency exomes 1,460/1,461,794 · genomes 1,094/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.39%	42
Admixed American	0.232%	432
South Asian	0.221%	453
Remaining individualsnot grpmax-eligible	0.219%	456
Finnishnot grpmax-eligible	0.131%	761
Middle Eastern	0.099%	1,010
European (non-Finnish)	0.0161%	6,211
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804

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.Ser370=
Coding: c.1110C>T
MANE Select: NM_145725
dbSNP: rs1051743
Type: single nucleotide variant
Location: chr14:102903404 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.26 · 10 PDB
Residue 370: 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); a turn

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.Ser370Asn 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
TRAF3 p.Arg25Cys 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-ser370 (accessed [today's date]).

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