Is TGFB1 p.Ile366= (c.1098C>A) pathogenic?

TGFB1 p.Ile366= (c.1098C>A) is classified Likely benign in TGFB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). No allele count reported in gnomAD v4.1 (AN 1,578,806).

How common is TGFB1 p.Ile366= (c.1098C>A) in the general population?

TGFB1 p.Ile366= (c.1098C>A) is no allele count reported in gnomAD v4.1 (AN 1,578,806) (gnomAD).

TGFB1 p.Ile366=

c.1098C>A · rs1477839489 · VCV2017324

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,578,806)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP -3.8, phastCons 1
Overall
CADD	9.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,578,806). 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: TGFB1
Protein: p.Ile366=
Coding: c.1098C>A
MANE Select: NM_000660
dbSNP: rs1477839489
Type: single nucleotide variant
Location: chr19:41331127 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 80.11 · 22 PDB
Residue 366: a β-strand

Full TGFB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TGFB1 p.Ile366Met Uncertain significance ★ ⚠ same residue
TGFB1 p.Ile366Thr Uncertain significance ★ ⚠ same residue
TGFB1 p.Ile366Val Uncertain significance ★ same residue
TGFB1 p.Arg218Cys Pathogenic ★★ same type
TGFB1 p.Arg218His Pathogenic/Likely pathogenic ★★ ⚠ same type
TGFB1 p.Tyr171Cys Likely pathogenic ★★ same type
TGFB1 c.1014+5G>A Uncertain significance ★★ same type
TGFB1 p.Arg152Trp Uncertain significance ★★ ⚠ 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/tgfb1-p-ile366 (accessed [today's date]).

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