Is TRAF6 p.Ser286Pro (c.856T>C) pathogenic?

TRAF6 p.Ser286Pro (c.856T>C) is classified Uncertain significance in TRAF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.0797); Ultra-rare (popmax 0.0145%, nfe).

How common is TRAF6 p.Ser286Pro (c.856T>C) in the general population?

TRAF6 p.Ser286Pro (c.856T>C) is ultra-rare (popmax 0.0145%, nfe) (gnomAD).

What do computational predictors say about TRAF6 p.Ser286Pro (c.856T>C)?

AlphaMissense predicts likely benign (score 0.0797) — an in-silico prediction, not a clinical call.

TRAF6 p.Ser286Pro

c.856T>C · rs147645716 · VCV2382318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0797 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0145%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0797	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -7.21	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 -0.33	GERP -3.4, phastCons 0.001
Regional constraint	o/e 0.70	unconstrained · MANE · 11 kb · p 2.5e-08 · regional, not allelic
Overall
CADD	0.063	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 0.0145% European (non-Finnish) · 171/1,180,044 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.012%

Overall 0.011% 178/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0145%	6,901
African / African-American	0.00534%	18,732
Remaining individualsnot grpmax-eligible	0.0032%	31,242
Admixed American	0.00167%	60,002

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: TRAF6
Protein: p.Ser286Pro
Coding: c.856T>C
MANE Select: NM_004620
dbSNP: rs147645716
Type: single nucleotide variant
Location: chr11:36490551 (GRCh38)
Gene constraint: LOEUF 0.356 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.30 · 13 PDB
Residue 286: the 'interaction with tax1bp1' region

Full TRAF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRAF6 p.Ala194Thr Uncertain significance ★ ⚠ same type
TRAF6 p.Arg167His Uncertain significance ★ ⚠ same type
TRAF6 p.Arg402His Uncertain significance ★ same type
TRAF6 p.Asn212Ser Uncertain significance ★ ⚠ same type
TRAF6 p.Asp181Ala Uncertain significance ★ ⚠ same type
TRAF6 p.Glu114Asp Uncertain significance ★ ⚠ same type
TRAF6 p.Glu144Lys Uncertain significance ★ ⚠ same type
TRAF6 p.Glu225Gln Uncertain significance ★ ⚠ same type

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/traf6-p-ser286pro (accessed [today's date]).

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