Is TRAF3IP2 p.Pro6Ala (c.16C>G) pathogenic?

TRAF3IP2 p.Pro6Ala (c.16C>G) is classified Uncertain significance in TRAF3IP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-10-14). AlphaMissense: ambiguous (0.3519); Very rare (popmax 8.48e-05%, nfe); Associated with candidiasis, familial, 8.

What condition is associated with TRAF3IP2 p.Pro6Ala (c.16C>G)?

TRAF3IP2 p.Pro6Ala (c.16C>G) is associated with candidiasis, familial, 8 (ClinVar).

How common is TRAF3IP2 p.Pro6Ala (c.16C>G) in the general population?

TRAF3IP2 p.Pro6Ala (c.16C>G) is very rare (popmax 8.48e-05%, nfe) (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.Pro6Ala (c.16C>G)?

AlphaMissense predicts ambiguous (score 0.3519) — an in-silico prediction, not a clinical call.

TRAF3IP2 p.Pro6Ala

c.16C>G · rs1471659672 · VCV663282

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3519 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

candidiasis, familial, 8

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3519	ambiguous
REVEL	0.221	benign-leaning
SaProt	LLR -6.69	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 19 kb · p 0.0015 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P15A vs ClinVar P6A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,756 alleles

Overall 0.000124% 2/1,613,818 alleles · very rare exomes 2/1,461,482 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,496
European (non-Finnish)grpmax	8.48e-05%	1,179,756

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro6Ala
Coding: c.16C>G
MANE Select: NM_147686
dbSNP: rs1471659672
Type: single nucleotide variant
Location: chr6:111592071 (GRCh38)

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

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-pro6ala (accessed [today's date]).

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