Is TAB2 p.Arg72His (c.215G>A) pathogenic?

TAB2 p.Arg72His (c.215G>A) is classified Uncertain significance in TAB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-01). AlphaMissense: likely benign (0.1006); Very rare (popmax 0.00695%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TAB2 p.Arg72His (c.215G>A)?

TAB2 p.Arg72His (c.215G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TAB2 p.Arg72His (c.215G>A) in the general population?

TAB2 p.Arg72His (c.215G>A) is very rare (popmax 0.00695%, nfe) (gnomAD).

What do computational predictors say about TAB2 p.Arg72His (c.215G>A)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

TAB2 p.Arg72His

c.215G>A · VCV3688383

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.483	indeterminate
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 20 kb · p 7.3e-06 · regional, not allelic
Overall
CADD	21.4	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 0.00695% European (non-Finnish) · 82/1,180,042 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00527% 85/1,614,032 alleles · very rare exomes 83/1,461,880 · genomes 2/152,152 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00695%	14,391
East Asian	0.00223%	44,890
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Arg72His
Coding: c.215G>A
MANE Select: NM_001292034
Type: single nucleotide variant
Location: chr6:149378130 (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.Arg72Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
TAB2 p.Ala618Val 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
TAB2 p.Glu93Lys 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-arg72his (accessed [today's date]).

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