Is TRAF2 p.Pro183Ser (c.547C>T) pathogenic?

TRAF2 p.Pro183Ser (c.547C>T) is classified Uncertain significance in TRAF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.1934); Ultra-rare (popmax 0.0164%, mid).

How common is TRAF2 p.Pro183Ser (c.547C>T) in the general population?

TRAF2 p.Pro183Ser (c.547C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about TRAF2 p.Pro183Ser (c.547C>T)?

AlphaMissense predicts likely benign (score 0.1934) — an in-silico prediction, not a clinical call.

TRAF2 p.Pro183Ser

c.547C>T · rs750248731 · VCV2491654

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1934 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1934	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -9.38	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 4.7	GERP 1.2, phastCons 1
Overall
CADD	24.8	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000929% 15/1,614,066 alleles · ultra-rare exomes 13/1,461,852 · genomes 2/152,214 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00769%	13,011
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00133%	74,928
European (non-Finnish)	0.000424%	236,009

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: TRAF2
Protein: p.Pro183Ser
Coding: c.547C>T
MANE Select: NM_021138
dbSNP: rs750248731
Type: single nucleotide variant
Location: chr9:136909938 (GRCh38)
Structure: AlphaFold pLDDT 60.31 · 3 PDB
Residue 183: the 'necessary for interaction with traf6' region; the 'traf family member interaction' region

Full TRAF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TANK p.Gln113Glu Benign ★★ same type
TRAF2 p.Arg308= Benign ★★ same type
TRAF2 p.Gly81= Benign ★★ same type
TRAF2 p.Phe361= Benign ★★ same type
TANK p.Arg40Ser Uncertain significance ★ ⚠ same type
TANK p.Arg42Cys Uncertain significance ★ ⚠ same type
TANK p.Asn87Ser Uncertain significance ★ ⚠ same type
TANK p.Asn88Ile 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/traf2-p-pro183ser (accessed [today's date]).

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