Is TGFBR3 p.Arg151= (c.453G>A) pathogenic?

TGFBR3 p.Arg151= (c.453G>A) is classified Likely benign in TGFBR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-11-01). Rare (popmax 0.195%, amr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with TGFBR3 p.Arg151= (c.453G>A)?

TGFBR3 p.Arg151= (c.453G>A) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is TGFBR3 p.Arg151= (c.453G>A) in the general population?

TGFBR3 p.Arg151= (c.453G>A) is rare (popmax 0.195%, amr) (gnomAD).

TGFBR3 p.Arg151=

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.453G>A · rs17883665 · VCV547815

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.195%, amr)

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 1.7	GERP 2, phastCons 0.31
Overall
CADD	12.48	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.195% Admixed American · 117/60,030 alleles

Filtering AF 0.166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.155%

Overall 0.0601% 970/1,614,158 alleles · rare exomes 870/1,461,864 · genomes 100/152,294 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.195%	513
European (non-Finnish)	0.0695%	1,439
Remaining individualsnot grpmax-eligible	0.0464%	2,156
African / African-American	0.00533%	18,758

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: TGFBR3
Protein: p.Arg151=
Coding: c.453G>A
MANE Select: NM_003243
dbSNP: rs17883665
Type: single nucleotide variant
Location: chr1:91734891 (GRCh38)
Gene constraint: LOEUF 0.636 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.58 · 1 PDB

Full TGFBR3 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

TGFBR3 p.Arg151Gly Uncertain significance ★ ⚠ same residue
TGFBR3 p.Asp255Glu Uncertain significance ★★ ⚠ same condition
TGFBR3 p.Pro777Ser Benign/Likely benign ★★ same condition
TGFBR3 p.Thr19Ala Benign/Likely benign ★★ same condition
TGFBR3 c.385-20C>T Likely benign ★ same condition
TGFBR3 c.1076-16CTT[2] Likely benign ★ same condition
TGFBR3 p.Ala72= Benign ★★ same type
TGFBR3 p.Gly765Arg Benign ★★ same type

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/tgfbr3-p-arg151 (accessed [today's date]).

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