Is TAB2 p.Glu49Lys (c.145G>A) pathogenic?

TAB2 p.Glu49Lys (c.145G>A) is classified Uncertain significance in TAB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.861); Very rare (popmax 0.000339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TAB2 p.Glu49Lys (c.145G>A)?

TAB2 p.Glu49Lys (c.145G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TAB2 p.Glu49Lys (c.145G>A) in the general population?

TAB2 p.Glu49Lys (c.145G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about TAB2 p.Glu49Lys (c.145G>A)?

AlphaMissense predicts likely pathogenic (score 0.861) — an in-silico prediction, not a clinical call.

TAB2 p.Glu49Lys

c.145G>A · rs376797713 · VCV1917778

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.861 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.861	likely pathogenic
REVEL	0.575	indeterminate
SaProt	LLR -10.15	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.26	acceptor loss at this position · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 20 kb · p 7.3e-06 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000339% European (non-Finnish) · 4/1,180,012 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,990 alleles · very rare exomes 3/1,461,828 · genomes 1/152,162 · joint denominator

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.Glu49Lys
Coding: c.145G>A
MANE Select: NM_001292034
dbSNP: rs376797713
Type: single nucleotide variant
Location: chr6:149378060 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 53.24 · 6 PDB
Residue 49: the cue domain; an α-helix

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.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.Glu93Lys Uncertain significance ★★ ⚠ same condition
TAB2 p.Gly56Ser 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-glu49lys (accessed [today's date]).

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