Is TBX5 p.Pro142= (c.426C>G) pathogenic?

TBX5 p.Pro142= (c.426C>G) is classified Likely benign in TBX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TBX5 p.Pro142= (c.426C>G)?

TBX5 p.Pro142= (c.426C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is TBX5 p.Pro142= (c.426C>G) in the general population?

TBX5 p.Pro142= (c.426C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

TBX5 p.Pro142=

c.426C>G · VCV3453926

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -14	GERP -3.9
Overall
CADD	0.244	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,050 alleles

Overall 6.2e-05% 1/1,613,048 alleles · very rare exomes 1/1,460,760 · genomes 0/152,288 · 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: TBX5
Protein: p.Pro142=
Coding: c.426C>G
MANE Select: NM_181486
Type: single nucleotide variant
Location: chr12:114398657 (GRCh38)
Gene constraint: LOEUF 0.267 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 63.38 · 4 PDB
Residue 142: a DNA-binding region; a β-strand

Full TBX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TBX5 p.Pro142Ser Uncertain significance ★ ⚠ same residue
TBX5 c.243-1G>A Pathogenic/Likely pathogenic ★★ same condition
TBX5 c.362+2T>C Pathogenic/Likely pathogenic ★★ same condition
TBX5 c.982+2T>G Pathogenic/Likely pathogenic ★★ same condition
TBX5 p.Arg237Trp Pathogenic ★★ same condition
TBX5 p.Ala143Thr Uncertain significance ★★ ⚠ same condition
TBX5 p.Ala210Pro Uncertain significance ★★ ⚠ same condition
TBX5 p.Ala2Thr 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/tbx5-p-pro142 (accessed [today's date]).

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