Is TRAF3IP2 p.Ser48= (c.144T>G) pathogenic?

TRAF3IP2 p.Ser48= (c.144T>G) is classified Likely benign in TRAF3IP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-18). Very rare (popmax 0.00525%, nfe); Associated with candidiasis, familial, 8.

What condition is associated with TRAF3IP2 p.Ser48= (c.144T>G)?

TRAF3IP2 p.Ser48= (c.144T>G) is associated with candidiasis, familial, 8 (ClinVar).

How common is TRAF3IP2 p.Ser48= (c.144T>G) in the general population?

TRAF3IP2 p.Ser48= (c.144T>G) is very rare (popmax 0.00525%, nfe) (gnomAD).

How is Chronic mucocutaneous candidiasis inherited?

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

TRAF3IP2 p.Ser48=

c.144T>G · rs957334802 · VCV2882738

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00525%, nfe)

Conditions

candidiasis, familial, 8

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 0.62	GERP -4.1, phastCons 0.004
Overall
CADD	4.361	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00525% European (non-Finnish) · 62/1,180,046 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00396% 64/1,614,244 alleles · very rare exomes 64/1,461,892 · genomes 0/152,352 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00525%	19,033
Remaining individualsnot grpmax-eligible	0.0032%	31,254

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.Ser48=
Coding: c.144T>G
MANE Select: NM_147686
dbSNP: rs957334802
Type: single nucleotide variant
Location: chr6:111591943 (GRCh38)
Gene constraint: LOEUF 0.771 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.91 · 1 PDB
Residue 48: 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.Ser48Phe 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
TRAF3IP2 p.Glu479Lys 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-ser48 (accessed [today's date]).

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