Is TGFB2 p.His360= (c.1080C>T) pathogenic?

TGFB2 p.His360= (c.1080C>T) is classified Likely benign in TGFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-15). Absent from gnomAD v4.1; Associated with Loeys-Dietz syndrome 4.

What condition is associated with TGFB2 p.His360= (c.1080C>T)?

TGFB2 p.His360= (c.1080C>T) is associated with Loeys-Dietz syndrome 4 (ClinVar).

How common is TGFB2 p.His360= (c.1080C>T) in the general population?

TGFB2 p.His360= (c.1080C>T) is absent from gnomAD v4.1 (gnomAD).

TGFB2 p.His360=

c.1080C>T · rs2102630189 · VCV1533818

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.018	GERP 0.26, phastCons 0.79
Overall
CADD	3.792	PHRED · no single calibrated threshold — expert panels disagree

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: TGFB2
Protein: p.His360=
Coding: c.1080C>T
MANE Select: NM_003238
dbSNP: rs2102630189
Type: single nucleotide variant
Location: chr1:218437490 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB
Residue 360: a disulfide bond; a UniProt-annotated variant site (in lds4); 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

Similar variants

TGFB2 p.His360Tyr 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-his360 (accessed [today's date]).

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