Is TBX3 p.Pro367= (c.1101C>G) pathogenic?

TBX3 p.Pro367= (c.1101C>G) is classified Benign in TBX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Ultra-rare (popmax 0.0182%, eas); Associated with ulnar-mammary syndrome.

What condition is associated with TBX3 p.Pro367= (c.1101C>G)?

TBX3 p.Pro367= (c.1101C>G) is associated with ulnar-mammary syndrome (ClinVar).

How common is TBX3 p.Pro367= (c.1101C>G) in the general population?

TBX3 p.Pro367= (c.1101C>G) is ultra-rare (popmax 0.0182%, eas) (gnomAD).

TBX3 p.Pro367=

c.1101C>G · rs761242306 · VCV307368

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, eas)

Conditions

ulnar-mammary syndrome

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 -13	GERP -4
Overall
CADD	0.101	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0182% East Asian · 8/44,064 alleles

Filtering AF 0.00898% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00651%

Overall 0.000882% 14/1,586,668 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0182%	5,508
Remaining individualsnot grpmax-eligible	0.00324%	30,885
South Asian	0.00227%	43,996
Admixed American	0.00176%	56,690
European (non-Finnish)	8.53e-05%	1,171,751

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.Pro367=
Coding: c.1101C>G
MANE Select: NM_005996
dbSNP: rs761242306
Type: single nucleotide variant
Location: chr12:114674774 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 0.99 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.55 · 1 PDB
Residue 367: the 'disordered' region

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

Disease context

ulnar-mammary syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TBX3 p.Gln475Ter Pathogenic ★★ same condition
TBX3 c.1710+3A>G Uncertain significance ★★ same condition
TBX3 p.Ala158Thr Uncertain significance ★★ ⚠ same condition
TBX3 p.Ala336Val Uncertain significance ★★ ⚠ same condition
TBX3 p.Ala357Pro Uncertain significance ★★ ⚠ same condition
TBX3 p.Ala391Gly Uncertain significance ★★ ⚠ same condition
TBX3 p.Ala470Thr Uncertain significance ★★ ⚠ same condition
TBX3 p.Ala488Thr 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-pro367 (accessed [today's date]).

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