Is TAB2 p.Ile613Thr (c.1838T>C) pathogenic?

TAB2 p.Ile613Thr (c.1838T>C) is classified Uncertain significance in TAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely pathogenic (0.9697); Very rare (popmax 8.48e-05%, nfe); Associated with congenital heart defects, multiple types, 2.

What condition is associated with TAB2 p.Ile613Thr (c.1838T>C)?

TAB2 p.Ile613Thr (c.1838T>C) is associated with congenital heart defects, multiple types, 2 (ClinVar).

How common is TAB2 p.Ile613Thr (c.1838T>C) in the general population?

TAB2 p.Ile613Thr (c.1838T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about TAB2 p.Ile613Thr (c.1838T>C)?

AlphaMissense predicts likely pathogenic (score 0.9697) — an in-silico prediction, not a clinical call.

TAB2 p.Ile613Thr

c.1838T>C · VCV3572964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital heart defects, multiple types, 2

Computational evidence

Protein change
AlphaMissense	0.9697	likely pathogenic
REVEL	0.629	indeterminate
SaProt	LLR -9.47	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 12 kb · p 7.4e-11 · regional, not allelic
Overall
CADD	24.5	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 8.48e-05% European (non-Finnish) · 1/1,179,864 alleles

Overall 6.2e-05% 1/1,613,790 alleles · very rare exomes 1/1,461,482 · genomes 0/152,308 · 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.Ile613Thr
Coding: c.1838T>C
MANE Select: NM_001292034
Type: single nucleotide variant
Location: chr6:149398042 (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

congenital heart defects, multiple types, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TAB2 c.1764+1G>A Pathogenic/Likely pathogenic ★★ same condition
TAB2 p.Arg574Ter Likely pathogenic ★★ same condition
TAB2 p.Arg96Lys Uncertain significance ★★ ⚠ same condition
TAB2 p.His6Arg Uncertain significance ★★ ⚠ same condition
TAB2 p.Ile68Thr Uncertain significance ★★ same condition
TAB2 p.Ser50Asn Uncertain significance ★★ ⚠ same condition
TAB2 p.Gln7= Benign/Likely benign ★★ same condition
TAB2 p.Gln127Ter Pathogenic ★ 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-ile613thr (accessed [today's date]).

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