Is TAB2 p.Pro208Ser (c.622C>T) pathogenic?

TAB2 p.Pro208Ser (c.622C>T) is classified Pathogenic in TAB2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2010-06-11). AlphaMissense: likely benign (0.1032); Very rare (popmax 0.000508%, nfe); Associated with congenital heart defects, multiple types, 2.

What condition is associated with TAB2 p.Pro208Ser (c.622C>T)?

TAB2 p.Pro208Ser (c.622C>T) is associated with congenital heart defects, multiple types, 2 (ClinVar).

How common is TAB2 p.Pro208Ser (c.622C>T) in the general population?

TAB2 p.Pro208Ser (c.622C>T) is very rare (popmax 0.000508%, nfe) (gnomAD).

What do computational predictors say about TAB2 p.Pro208Ser (c.622C>T)?

AlphaMissense predicts likely benign (score 0.1032) — an in-silico prediction, not a clinical call.

TAB2 p.Pro208Ser

c.622C>T · rs267607101 · VCV5211

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1032 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

congenital heart defects, multiple types, 2

Computational evidence

Protein change
AlphaMissense	0.1032	likely benign ⚠ discordant with ClinVar
REVEL	0.4	indeterminate
SaProt	LLR -5.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; 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	17.5	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 0.000508% European (non-Finnish) · 6/1,180,036 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,120 alleles · very rare exomes 6/1,461,800 · genomes 0/152,320 · 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.Pro208Ser
Coding: c.622C>T
MANE Select: NM_001292034
dbSNP: rs267607101
Type: single nucleotide variant
Location: chr6:149378537 (GRCh38)
Gene constraint: LOEUF 0.117 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 53.24 · 6 PDB
Residue 208: a UniProt-annotated variant site (in chtd2)

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 p.Pro208fs Pathogenic ★ same residue
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

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-pro208ser (accessed [today's date]).

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