Is TRAF3 p.Ala484Val (c.1451C>T) pathogenic?

TRAF3 p.Ala484Val (c.1451C>T) is classified Uncertain significance in TRAF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-06). AlphaMissense: likely pathogenic (0.7859); Absent from gnomAD v4.1; Associated with herpes simplex encephalitis, susceptibility to, 3.

What condition is associated with TRAF3 p.Ala484Val (c.1451C>T)?

TRAF3 p.Ala484Val (c.1451C>T) is associated with herpes simplex encephalitis, susceptibility to, 3 (ClinVar).

How common is TRAF3 p.Ala484Val (c.1451C>T) in the general population?

TRAF3 p.Ala484Val (c.1451C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TRAF3 p.Ala484Val (c.1451C>T)?

AlphaMissense predicts likely pathogenic (score 0.7859) — an in-silico prediction, not a clinical call.

TRAF3 p.Ala484Val

c.1451C>T · VCV3649042

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7859 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

herpes simplex encephalitis, susceptibility to, 3

Computational evidence

Protein change
AlphaMissense	0.7859	likely pathogenic
REVEL	0.466	indeterminate
SaProt	LLR -9.11	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 277 bp · p 1.8e-08 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TRAF3
Protein: p.Ala484Val
Coding: c.1451C>T
MANE Select: NM_145725
Type: single nucleotide variant
Location: chr14:102905528 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.26 · 10 PDB
Residue 484: the math domain; 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 UniProt-annotated variant site (in imd132b; likely pathogenic); an α-helix

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.Ala484Thr 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-ala484val (accessed [today's date]).

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