Is TGFB2 p.Arg34Cys (c.100C>T) pathogenic?

TGFB2 p.Arg34Cys (c.100C>T) is classified Uncertain significance in TGFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-07). AlphaMissense: ambiguous (0.5269); Absent from gnomAD v4.1; Associated with Loeys-Dietz syndrome 4.

What condition is associated with TGFB2 p.Arg34Cys (c.100C>T)?

TGFB2 p.Arg34Cys (c.100C>T) is associated with Loeys-Dietz syndrome 4 (ClinVar).

How common is TGFB2 p.Arg34Cys (c.100C>T) in the general population?

TGFB2 p.Arg34Cys (c.100C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TGFB2 p.Arg34Cys (c.100C>T)?

AlphaMissense predicts ambiguous (score 0.5269) — an in-silico prediction, not a clinical call.

TGFB2 p.Arg34Cys

c.100C>T · rs1571820734 · VCV656106

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5269 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Loeys-Dietz syndrome 4

Computational evidence

Protein change
AlphaMissense	0.5269	ambiguous
REVEL	0.419	indeterminate
SaProt	LLR -12.08	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 95 kb · p 2.1e-08 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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: TGFB2
Protein: p.Arg34Cys
Coding: c.100C>T
MANE Select: NM_003238
dbSNP: rs1571820734
Type: single nucleotide variant
Location: chr1:218346801 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB
Residue 34: 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.Arg34His 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-arg34cys (accessed [today's date]).

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