Is TRAF3 p.Ala27Pro (c.79G>C) pathogenic?

TRAF3 p.Ala27Pro (c.79G>C) is classified Uncertain significance in TRAF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-15). AlphaMissense: likely benign (0.0701); Rare (popmax 0.107%, eas); Associated with herpes simplex encephalitis, susceptibility to, 3.

What condition is associated with TRAF3 p.Ala27Pro (c.79G>C)?

TRAF3 p.Ala27Pro (c.79G>C) is associated with herpes simplex encephalitis, susceptibility to, 3 (ClinVar).

How common is TRAF3 p.Ala27Pro (c.79G>C) in the general population?

TRAF3 p.Ala27Pro (c.79G>C) is rare (popmax 0.107%, eas) (gnomAD).

What do computational predictors say about TRAF3 p.Ala27Pro (c.79G>C)?

AlphaMissense predicts likely benign (score 0.0701) — an in-silico prediction, not a clinical call.

TRAF3 p.Ala27Pro

c.79G>C · rs759772207 · VCV2197071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0701 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.107%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

herpes simplex encephalitis, susceptibility to, 3

Computational evidence

Protein change
AlphaMissense	0.0701	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -3.3
Regional constraint	o/e 1.05	unconstrained · MANE · 84 bp · p 0.78 · regional, not allelic
Overall
CADD	0.265	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.107% East Asian · 48/44,890 alleles

Filtering AF 0.0828% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0743%

Overall 0.00304% 49/1,614,096 alleles · rare exomes 46/1,461,894 · genomes 3/152,202 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.107%	935
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Ala27Pro
Coding: c.79G>C
MANE Select: NM_145725
dbSNP: rs759772207
Type: single nucleotide variant
Location: chr14:102870280 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 88.26 · 10 PDB
Residue 27: 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.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
TRAF3 p.Arg338Gln 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-ala27pro (accessed [today's date]).

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