Is TRAF3IP2 p.Ser57Pro (c.169T>C) pathogenic?

TRAF3IP2 p.Ser57Pro (c.169T>C) is classified Uncertain significance in TRAF3IP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). AlphaMissense: likely benign (0.0633); Rare (popmax 0.163%, eas); Associated with candidiasis, familial, 8.

What condition is associated with TRAF3IP2 p.Ser57Pro (c.169T>C)?

TRAF3IP2 p.Ser57Pro (c.169T>C) is associated with candidiasis, familial, 8 (ClinVar).

How common is TRAF3IP2 p.Ser57Pro (c.169T>C) in the general population?

TRAF3IP2 p.Ser57Pro (c.169T>C) is rare (popmax 0.163%, eas) (gnomAD).

How is Chronic mucocutaneous candidiasis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TRAF3IP2 p.Ser57Pro (c.169T>C)?

AlphaMissense predicts likely benign (score 0.0633) — an in-silico prediction, not a clinical call.

TRAF3IP2 p.Ser57Pro

c.169T>C · rs754326983 · VCV2066389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0633 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.163%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

candidiasis, familial, 8

Computational evidence

Protein change
AlphaMissense	0.0633	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.29	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 0.21	GERP -4, phastCons 0.21
Regional constraint	o/e 0.86	unconstrained · MANE · 19 kb · p 0.0015 · regional, not allelic
Overall
CADD	0.396	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S66P vs ClinVar S57P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% East Asian · 73/44,894 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.122%

Overall 0.00489% 79/1,614,096 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.163%	615
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	8.47e-05%	1,180,048

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: TRAF3IP2
Protein: p.Ser57Pro
Coding: c.169T>C
MANE Select: NM_147686
dbSNP: rs754326983
Type: single nucleotide variant
Location: chr6:111591918 (GRCh38)
Gene constraint: LOEUF 0.771 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.91 · 1 PDB
Residue 57: the 'mediates interaction with traf6' region; the 'disordered' region

Full TRAF3IP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

candidiasis, familial, 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Chronic mucocutaneous candidiasis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy

Similar variants

TRAF3IP2 p.Ser57= Likely benign ★ same residue
TRAF3IP2 p.Ser57Phe Uncertain significance ★ ⚠ same residue
TRAF3IP2 c.1201+1G>C Likely pathogenic ★★ same condition
TRAF3IP2 p.Ala328Thr Uncertain significance ★★ ⚠ same condition
TRAF3IP2 p.Ala36Val Uncertain significance ★★ ⚠ same condition
TRAF3IP2 p.Ala473Thr Uncertain significance ★★ ⚠ same condition
TRAF3IP2 p.Asn45Lys Uncertain significance ★★ ⚠ same condition
TRAF3IP2 p.Gln18His 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/traf3ip2-p-ser57pro (accessed [today's date]).

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