Is TGFB2 p.Arg84= (c.252G>A) pathogenic?

TGFB2 p.Arg84= (c.252G>A) is classified Likely benign in TGFB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-23). Ultra-rare (popmax 0.0107%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

How common is TGFB2 p.Arg84= (c.252G>A) in the general population?

TGFB2 p.Arg84= (c.252G>A) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

TGFB2 p.Arg84=

Q: What condition is associated with TGFB2 p.Arg84= (c.252G>A)?

TGFB2 p.Arg84= (c.252G>A) is associated with familial thoracic aortic aneurysm and aortic dissection, Loeys-Dietz syndrome 4 (ClinVar).

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.252G>A · rs952595114 · VCV1792670

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

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 -0.11	GERP -4.1, phastCons 0.01
Overall
CADD	9.508	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,942 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000806% 13/1,613,902 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,368
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.000339%	294,992

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.Arg84=
Coding: c.252G>A
MANE Select: NM_003238
dbSNP: rs952595114
Type: single nucleotide variant
Location: chr1:218346953 (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

Also linked: Loeys-Dietz syndrome 4

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

TGFB2 p.Arg84Gln Uncertain significance ★★ ⚠ 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
TGFB2 p.Arg299Gln 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-arg84 (accessed [today's date]).

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