Is TGFB2 p.Pro54= (c.162A>G) pathogenic?

TGFB2 p.Pro54= (c.162A>G) is classified Likely benign in TGFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-26). Very rare (popmax 0.00223%, eas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with TGFB2 p.Pro54= (c.162A>G)?

TGFB2 p.Pro54= (c.162A>G) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is TGFB2 p.Pro54= (c.162A>G) in the general population?

TGFB2 p.Pro54= (c.162A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

TGFB2 p.Pro54=

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.162A>G · rs769913843 · VCV1776776

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

familial thoracic aortic aneurysm and aortic dissection

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 0.053	GERP -4.1, phastCons 0.22
Overall
CADD	10.49	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,860 alleles

Overall 0.000124% 2/1,614,148 alleles · very rare exomes 2/1,461,892 · genomes 0/152,256 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,860
European (non-Finnish)	8.47e-05%	1,180,026

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.Pro54=
Coding: c.162A>G
MANE Select: NM_003238
dbSNP: rs769913843
Type: single nucleotide variant
Location: chr1:218346863 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB

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

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

TGFB2 c.346+1G>T Likely pathogenic ★★ same condition
TGFB2 p.Arg131Ter Pathogenic/Likely pathogenic ★★ same condition
TGFB2 p.Arg299Gln Pathogenic/Likely pathogenic ★★ same condition
TGFB2 p.Arg299Trp Pathogenic/Likely pathogenic ★★ same condition
TGFB2 p.Arg302Cys Pathogenic/Likely pathogenic ★★ same condition
TGFB2 p.Arg302His Pathogenic/Likely pathogenic ★★ same condition
TGFB2 p.Arg320Cys Pathogenic/Likely pathogenic ★★ same condition
TGFB2 p.Tyr341Ter 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-pro54 (accessed [today's date]).

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