Is TAB2 p.Arg546Ter (c.1636C>T) pathogenic?

TAB2 p.Arg546Ter (c.1636C>T) is classified Pathogenic/Likely pathogenic in TAB2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-16). No allele count reported in gnomAD v4.1 (AN 1,613,826); Associated with TAB2-related disorder.

What condition is associated with TAB2 p.Arg546Ter (c.1636C>T)?

TAB2 p.Arg546Ter (c.1636C>T) is associated with TAB2-related disorder (ClinVar).

How common is TAB2 p.Arg546Ter (c.1636C>T) in the general population?

TAB2 p.Arg546Ter (c.1636C>T) is no allele count reported in gnomAD v4.1 (AN 1,613,826) (gnomAD).

TAB2 p.Arg546Ter

c.1636C>T · rs1782216591 · VCV1199210

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,826)

Conditions

TAB2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 4 of 7
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP 0.83, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,826). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TAB2
Protein: p.Arg546Ter
Coding: c.1636C>T
MANE Select: NM_001292034
dbSNP: rs1782216591
Type: single nucleotide variant
Location: chr6:149397636 (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

TAB2-related disorder

Similar variants

TAB2 p.Gln170Lys Uncertain significance ★★ ⚠ same condition
TAB2 p.Gln111Ter Likely pathogenic ★ same condition
TAB2 c.102+1G>A Uncertain significance ★ same condition
TAB2 p.Cys684Ser Uncertain significance ★ ⚠ same condition
TAB2 p.Gly210Glu Uncertain significance ⚠ same condition
TAB2 p.His89fs Likely pathogenic ★ same condition
TAB2 p.Val27fs Likely pathogenic ★ same condition
TAB2 c.1764+8_1764+9insAT Likely benign 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-arg546ter (accessed [today's date]).

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