Is TGFB2 p.Arg36= (c.106A>C) pathogenic?

TGFB2 p.Arg36= (c.106A>C) is classified Likely benign in TGFB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-16). Very rare (popmax 0.00167%, amr); Associated with Loeys-Dietz syndrome 4.

What condition is associated with TGFB2 p.Arg36= (c.106A>C)?

TGFB2 p.Arg36= (c.106A>C) is associated with Loeys-Dietz syndrome 4, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is TGFB2 p.Arg36= (c.106A>C) in the general population?

TGFB2 p.Arg36= (c.106A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

TGFB2 p.Arg36=

c.106A>C · rs10482720 · VCV1782854

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Loeys-Dietz syndrome 4

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 5.7	GERP 0.84, phastCons 1
Overall
CADD	13.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,020 alleles

Overall 0.000137% 2/1,461,892 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,020
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Arg36=
Coding: c.106A>C
MANE Select: NM_003238
dbSNP: rs10482720
Type: single nucleotide variant
Location: chr1:218346807 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB
Residue 36: a UniProt-annotated variant site (in caend2; likely pathogenic; results in increased signal transduction when tested in a luciferase reporter assay; increased tgfb2 secretion); a UniProt-annotated variant site (in caend2; likely pathogenic); an α-helix

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

Disease context

Loeys-Dietz syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

Similar variants

TGFB2 p.Arg36Gly 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-arg36 (accessed [today's date]).

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