Is TGFBR2 p.Ala232= (c.696C>T) pathogenic?

TGFBR2 p.Ala232= (c.696C>T) is classified Likely benign in TGFBR2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-09). Ultra-rare (popmax 0.0274%, sas); Associated with Loeys-Dietz syndrome 2.

What condition is associated with TGFBR2 p.Ala232= (c.696C>T)?

TGFBR2 p.Ala232= (c.696C>T) is associated with Loeys-Dietz syndrome 2, familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is TGFBR2 p.Ala232= (c.696C>T) in the general population?

TGFBR2 p.Ala232= (c.696C>T) is ultra-rare (popmax 0.0274%, sas) (gnomAD).

TGFBR2 p.Ala232=

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.696C>T · rs768508812 · VCV344659

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

Conditions

Loeys-Dietz syndrome 2

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 4.9	GERP 2.1, phastCons 1
Overall
CADD	13.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0274% South Asian · 25/91,082 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00192% 31/1,614,208 alleles · ultra-rare exomes 30/1,461,878 · genomes 1/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0274%	3,643
Remaining individualsnot grpmax-eligible	0.0032%	31,256
European (non-Finnish)	0.000339%	295,008

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: TGFBR2
Protein: p.Ala232=
Coding: c.696C>T
MANE Select: NM_003242
dbSNP: rs768508812
Type: single nucleotide variant
Location: chr3:30671879 (GRCh38)
Gene constraint: LOEUF 0.531 · pLI 0.91 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 81.22 · 22 PDB

Full TGFBR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Loeys-Dietz syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial thoracic aortic aneurysm and aortic dissection

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

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

TGFBR2 p.Ala414Pro Pathogenic/Likely pathogenic ★★ same condition
TGFBR2 p.Ala527Thr Likely pathogenic ★★ same condition
TGFBR2 p.Ala527Val Pathogenic/Likely pathogenic ★★ same condition
TGFBR2 p.Arg356Pro Pathogenic/Likely pathogenic ★★ same condition
TGFBR2 p.Arg378Ser Pathogenic/Likely pathogenic ★★ same condition
TGFBR2 p.Arg460Cys Pathogenic ★★ same condition
TGFBR2 p.Arg460Gly Pathogenic ★★ same condition
TGFBR2 p.Arg460His 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/tgfbr2-p-ala232 (accessed [today's date]).

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