Is TGFB1 p.Arg255= (c.765G>A) pathogenic?

TGFB1 p.Arg255= (c.765G>A) is classified Likely benign in TGFB1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-03). Absent from gnomAD v4.1.

How common is TGFB1 p.Arg255= (c.765G>A) in the general population?

TGFB1 p.Arg255= (c.765G>A) is absent from gnomAD v4.1 (gnomAD).

TGFB1 p.Arg255=

c.765G>A · rs973558315 · VCV1568573

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.13	GERP -3.3, phastCons 0.94
Overall
CADD	9.304	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: TGFB1
Protein: p.Arg255=
Coding: c.765G>A
MANE Select: NM_000660
dbSNP: rs973558315
Type: single nucleotide variant
Location: chr19:41341978 (GRCh38)
Gene constraint: LOEUF 0.682 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 80.11 · 22 PDB
Residue 255: the 'arm domain' region

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

Similar variants

TGFB1 p.Arg255Gln Uncertain significance ★ ⚠ same residue
TGFB1 p.Arg255Leu Uncertain significance ★ ⚠ same residue
TGFB1 p.Arg255Trp 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-arg255 (accessed [today's date]).

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