Is TBX3 p.Pro191= (c.573C>T) pathogenic?

TBX3 p.Pro191= (c.573C>T) is classified Likely benign in TBX3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-18). Ultra-rare (popmax 0.0165%, mid); Associated with TBX3-related disorder.

What condition is associated with TBX3 p.Pro191= (c.573C>T)?

TBX3 p.Pro191= (c.573C>T) is associated with TBX3-related disorder (ClinVar).

How common is TBX3 p.Pro191= (c.573C>T) in the general population?

TBX3 p.Pro191= (c.573C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

TBX3 p.Pro191=

c.573C>T · VCV3351661

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

TBX3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11	GERP -4.4
Overall
CADD	1.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

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

Overall 0.000752% 11/1,461,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,254
East Asian	0.00223%	44,878
African / African-American	0.00133%	74,970
European (non-Finnish)	0.000508%	196,669

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: TBX3
Protein: p.Pro191=
Coding: c.573C>T
MANE Select: NM_005996
Type: single nucleotide variant
Location: chr12:114680963 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.55 · 1 PDB
Residue 191: a DNA-binding region; a β-strand

Full TBX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

TBX3-related disorder

Similar variants

TBX3 c.1710+1G>A Likely pathogenic ★ same condition
TBX3 p.Glu381Ter Pathogenic ★ same condition
TBX3 p.Met123Ile Likely pathogenic ★ same condition
TBX3 c.658-297G>A Uncertain significance ★ ⚠ same condition
TBX3 p.Ala192Thr Uncertain significance ★ ⚠ same condition
TBX3 c.390-1G>A Likely pathogenic same condition
TBX3 c.657+1G>A Pathogenic same condition
TBX3 c.658-262G>A 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/tbx3-p-pro191 (accessed [today's date]).

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