Is TGFBR2 p.Arg207Pro (c.620G>C) pathogenic?

TGFBR2 p.Arg207Pro (c.620G>C) is classified Uncertain significance in TGFBR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely benign (0.1473); Absent from gnomAD v4.1; Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with TGFBR2 p.Arg207Pro (c.620G>C)?

TGFBR2 p.Arg207Pro (c.620G>C) is associated with familial thoracic aortic aneurysm and aortic dissection (ClinVar).

How common is TGFBR2 p.Arg207Pro (c.620G>C) in the general population?

TGFBR2 p.Arg207Pro (c.620G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TGFBR2 p.Arg207Pro (c.620G>C)?

AlphaMissense predicts likely benign (score 0.1473) — an in-silico prediction, not a clinical call.

TGFBR2 p.Arg207Pro

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.620G>C · rs371209879 · VCV919447

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1473 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
AlphaMissense	0.1473	likely benign
REVEL	0.248	benign-leaning
SaProt	LLR -5.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 3, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 65 kb · p 3e-06 · regional, not allelic
Overall
CADD	19.66	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TGFBR2
Protein: p.Arg207Pro
Coding: c.620G>C
MANE Select: NM_003242
dbSNP: rs371209879
Type: single nucleotide variant
Location: chr3:30671803 (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

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

TGFBR2 p.Arg207Trp Uncertain significance ★★ ⚠ same residue
TGFBR2 p.Arg207= Likely benign ★★ same residue
TGFBR2 p.Arg207Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
TGFBR2 p.Arg207Leu Uncertain significance ★ ⚠ same residue
TGFBR2 p.Arg207Gly Uncertain significance ★ ⚠ same residue
TGFBR2 p.Ala414Pro Pathogenic/Likely pathogenic ★★ same condition
TGFBR2 p.Ala527Thr Likely pathogenic ★★ same condition
TGFBR2 p.Ala527Val 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/tgfbr2-p-arg207pro (accessed [today's date]).

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