Is TGFB3 p.Phe32fs (c.95_96insA) pathogenic?

TGFB3 p.Phe32fs (c.9596insA) is classified Pathogenic in TGFB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-04). No gnomAD frequency available for this variant; Associated with Rienhoff syndrome.

What condition is associated with TGFB3 p.Phe32fs (c.95_96insA)?

TGFB3 p.Phe32fs (c.95_96insA) is associated with Rienhoff syndrome (ClinVar).

How common is TGFB3 p.Phe32fs (c.95_96insA) in the general population?

TGFB3 p.Phe32fs (c.95_96insA) is no gnomAD frequency available for this variant (gnomAD).

TGFB3 p.Phe32fs

c.95_96insA · rs2503024114 · VCV2029032

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Rienhoff syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.85	GERP -3.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: TGFB3
Protein: p.Phe32fs
Coding: c.95_96insA
MANE Select: NM_003239
dbSNP: rs2503024114
Type: Insertion
Location: chr14:75980798 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 11 PDB
Residue 32: an α-helix

Full TGFB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Rienhoff syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TGFB3 p.Phe32Ile Uncertain significance ★★ ⚠ same residue
TGFB3 p.Phe32= Benign/Likely benign ★★ same residue
TGFB3 p.Phe32Leu Uncertain significance ★★ ⚠ same residue
TGFB3 p.Cys409delinsPhePhePhePhePhePhePheXaaXaaXaaXaaLeuValIleArgProProArgProProLysValLeuGlyLeuGlnAlaTer Uncertain significance ★ same condition
TGFB3 c.353-13_353-12insA Likely benign ★ same condition
TGFB3 c.517-2A>G Likely pathogenic ★★ same condition
TGFB3 c.646+1G>C Likely pathogenic ★★ same condition
TGFB3 c.926+1G>A 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/tgfb3-p-phe32fs (accessed [today's date]).

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