Is TGFB2 p.Arg320fs (c.959del) pathogenic?

TGFB2 p.Arg320fs (c.959del) is classified Pathogenic in TGFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-10). Absent from gnomAD; Associated with Loeys-Dietz syndrome 4.

What condition is associated with TGFB2 p.Arg320fs (c.959del)?

TGFB2 p.Arg320fs (c.959del) is associated with Loeys-Dietz syndrome 4 (ClinVar).

How common is TGFB2 p.Arg320fs (c.959del) in the general population?

TGFB2 p.Arg320fs (c.959del) is absent from gnomAD (gnomAD).

TGFB2 p.Arg320fs

c.959del · rs2464877339 · VCV2899783

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Loeys-Dietz syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TGFB2
Protein: p.Arg320fs
Coding: c.959del
MANE Select: NM_003238
dbSNP: rs2464877339
Type: Deletion
Location: chr1:218437369 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB
Residue 320: a UniProt-annotated variant site (in lds4); a UniProt-annotated variant site (in lds4; likely pathogenic; patients have minor signs of connective tissue disease); a β-strand; a disulfide bond

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

Similar variants

TGFB2 p.Arg320Cys Pathogenic/Likely pathogenic ★★ same residue
TGFB2 p.Arg320His Uncertain significance ★ ⚠ same residue
TGFB2 p.Arg193fs Pathogenic/Likely pathogenic ★★ same condition
TGFB2 p.Asn274fs Pathogenic ★★ same condition
TGFB2 p.Asp357fs Pathogenic/Likely pathogenic ★★ same condition
TGFB2 p.Ala147del Uncertain significance ★★ same condition
TGFB2 p.Leu391_Tyr392insTer Uncertain significance ★★ same condition
TGFB2 c.933-6del Benign/Likely benign ★★ 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-arg320fs (accessed [today's date]).

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