Is TG p.Phe476fs (c.1425_1426dup) pathogenic?

TG p.Phe476fs (c.14251426dup) is classified Likely pathogenic in TG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-18). Associated with thyroid dyshormonogenesis 3.

What condition is associated with TG p.Phe476fs (c.1425_1426dup)?

TG p.Phe476fs (c.1425_1426dup) is associated with thyroid dyshormonogenesis 3, autoimmune thyroid disease, susceptibility to, 3 (ClinVar).

How is Familial thyroid dyshormonogenesis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TG p.Phe476fs

c.1425_1426dup · VCV3595251

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

thyroid dyshormonogenesis 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP -2.5, phastCons 0.6

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

Variant & gene context

Gene: TG
Protein: p.Phe476fs
Coding: c.1425_1426dup
MANE Select: NM_003235
Type: Duplication
Location: chr8:132886796 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 476: an α-helix

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

Disease context

thyroid dyshormonogenesis 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autoimmune thyroid disease, susceptibility to, 3

For Familial thyroid dyshormonogenesis (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

TG p.Ala2613fs Likely pathogenic ★ same condition
TG p.Cys358fs Likely pathogenic ★ same condition
TG p.Gln502fs Likely pathogenic ★ same condition
TG p.Ile1790fs Likely pathogenic ★ same condition
TG p.Ser756fs Likely pathogenic ★ same condition
TG p.Val90fs Pathogenic ★ same condition
TG c.274+2T>G Pathogenic ★★ same condition
TG c.3634+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/tg-p-phe476fs (accessed [today's date]).

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