Is TGFB2 p.Val17= (c.51C>T) pathogenic?

TGFB2 p.Val17= (c.51C>T) is classified Likely benign in TGFB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). Ultra-rare (popmax 0.0121%, sas); Associated with Loeys-Dietz syndrome 4.

What condition is associated with TGFB2 p.Val17= (c.51C>T)?

TGFB2 p.Val17= (c.51C>T) is associated with Loeys-Dietz syndrome 4 (ClinVar).

How common is TGFB2 p.Val17= (c.51C>T) in the general population?

TGFB2 p.Val17= (c.51C>T) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

TGFB2 p.Val17=

c.51C>T · VCV3713387

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Conditions

Loeys-Dietz syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.42	GERP -4.1, phastCons 0.029
Overall
CADD	5.562	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,046 alleles

Filtering AF 0.00677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.000929% 15/1,614,084 alleles · ultra-rare exomes 14/1,461,812 · genomes 1/152,272 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,277
Remaining individualsnot grpmax-eligible	0.0064%	15,627

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TGFB2
Protein: p.Val17=
Coding: c.51C>T
MANE Select: NM_003238
Type: single nucleotide variant
Location: chr1:218346752 (GRCh38)
Gene constraint: LOEUF 0.463 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.41 · 11 PDB

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.Val17Ile 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-val17 (accessed [today's date]).

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