Is TGFB2 p.Pro119= (c.357G>A) pathogenic?

TGFB2 p.Pro119= (c.357G>A) is classified Benign/Likely benign in TGFB2 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-01-17). Rare (popmax 0.141%, sas); Associated with connective tissue disorder.

What condition is associated with TGFB2 p.Pro119= (c.357G>A)?

TGFB2 p.Pro119= (c.357G>A) is associated with connective tissue disorder, Loeys-Dietz syndrome 4, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is TGFB2 p.Pro119= (c.357G>A) in the general population?

TGFB2 p.Pro119= (c.357G>A) is rare (popmax 0.141%, sas) (gnomAD).

TGFB2 p.Pro119=

c.357G>A · rs138514914 · VCV213836

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.141%, sas)

Conditions

connective tissue disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.54	GERP -3.1, phastCons 0.99
Overall
CADD	14.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.141% South Asian · 124/88,048 alleles

Filtering AF 0.121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.113%

Overall 0.054% 854/1,582,866 alleles · rare exomes 771/1,430,906 · genomes 83/151,960 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.69%	59
South Asiangrpmax	0.141%	710
Remaining individualsnot grpmax-eligible	0.14%	717
Middle Eastern	0.0339%	2,953
European (non-Finnish)	0.0133%	7,533
Finnishnot grpmax-eligible	0.00473%	21,126
East Asian	0.00452%	22,128
Admixed American	0.0035%	28,546
African / African-American	0.00271%	36,878

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TGFB2
Protein: p.Pro119=
Coding: c.357G>A
MANE Select: NM_003238
dbSNP: rs138514914
Type: single nucleotide variant
Location: chr1:218405179 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB
Residue 119: a UniProt-annotated variant site (in lds4)

Full TGFB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Loeys-Dietz syndrome 4 familial thoracic aortic aneurysm and aortic dissection Ehlers-Danlos syndrome

Similar variants

TGFB2 p.Pro119Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
TGFB2 p.Pro119Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TGFB2 c.346+1G>A Pathogenic/Likely pathogenic ★★ same condition
TGFB2 c.346+1G>T Likely pathogenic ★★ same condition
TGFB2 c.510+1G>A Likely pathogenic ★★ same condition
TGFB2 c.932+1G>A Pathogenic/Likely pathogenic ★★ same condition
TGFB2 c.933-1G>A Pathogenic/Likely pathogenic ★★ same condition
TGFB2 p.Arg131Ter Pathogenic/Likely 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/tgfb2-p-pro119 (accessed [today's date]).

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