Is TAB2 p.Pro183Leu (c.548C>T) pathogenic?

TAB2 p.Pro183Leu (c.548C>T) is classified Likely pathogenic in TAB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely pathogenic (0.9343); Absent from gnomAD v4.1; Associated with congenital heart defects, multiple types, 2.

What condition is associated with TAB2 p.Pro183Leu (c.548C>T)?

TAB2 p.Pro183Leu (c.548C>T) is associated with congenital heart defects, multiple types, 2 (ClinVar).

How common is TAB2 p.Pro183Leu (c.548C>T) in the general population?

TAB2 p.Pro183Leu (c.548C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TAB2 p.Pro183Leu (c.548C>T)?

AlphaMissense predicts likely pathogenic (score 0.9343) — an in-silico prediction, not a clinical call.

TAB2 p.Pro183Leu

c.548C>T · rs2483386818 · VCV1708259

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9343 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

congenital heart defects, multiple types, 2

Computational evidence

Protein change
AlphaMissense	0.9343	likely pathogenic ✓ concordant with ClinVar
REVEL	0.462	indeterminate
SaProt	LLR -11.16	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 20 kb · p 7.3e-06 · regional, not allelic
Overall
CADD	23.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TAB2
Protein: p.Pro183Leu
Coding: c.548C>T
MANE Select: NM_001292034
dbSNP: rs2483386818
Type: single nucleotide variant
Location: chr6:149378463 (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-pro183leu (accessed [today's date]).

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