Is TAB2 p.Arg189His (c.566G>A) pathogenic?

TAB2 p.Arg189His (c.566G>A) is classified Conflicting classifications of pathogenicity in TAB2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-02-01). AlphaMissense: likely benign (0.1306); Ultra-rare (popmax 0.0133%, afr); Associated with Inborn genetic diseases.

What condition is associated with TAB2 p.Arg189His (c.566G>A)?

TAB2 p.Arg189His (c.566G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TAB2 p.Arg189His (c.566G>A) in the general population?

TAB2 p.Arg189His (c.566G>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about TAB2 p.Arg189His (c.566G>A)?

AlphaMissense predicts likely benign (score 0.1306) — an in-silico prediction, not a clinical call.

TAB2 p.Arg189His

c.566G>A · rs369027697 · VCV1428421

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1306 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1306	likely benign
REVEL	0.494	indeterminate
SaProt	LLR -6.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 20 kb · p 7.3e-06 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/75,026 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00322% 52/1,614,122 alleles · ultra-rare exomes 47/1,461,864 · genomes 5/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,503
Admixed American	0.00833%	12,004
Remaining individualsnot grpmax-eligible	0.0032%	31,255
European (non-Finnish)	0.00288%	34,707
South Asian	0.0011%	91,070

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: TAB2
Protein: p.Arg189His
Coding: c.566G>A
MANE Select: NM_001292034
dbSNP: rs369027697
Type: single nucleotide variant
Location: chr6:149378481 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 53.24 · 6 PDB

Full TAB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TAB2 p.Arg189Cys Uncertain significance ★ ⚠ same residue
TAB2 p.Ala618Val Uncertain significance ★★ ⚠ same condition
TAB2 p.Arg72His Uncertain significance ★★ ⚠ same condition
TAB2 p.Arg96Ser Uncertain significance ★★ same condition
TAB2 p.Asn118Tyr Uncertain significance ★★ ⚠ same condition
TAB2 p.Asn669Thr Uncertain significance ★★ ⚠ same condition
TAB2 p.Gln209Lys Uncertain significance ★★ ⚠ same condition
TAB2 p.Glu49Lys 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/tab2-p-arg189his (accessed [today's date]).

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