Is TG p.Ile444= (c.1332C>T) pathogenic?

TG p.Ile444= (c.1332C>T) is classified Benign/Likely benign in TG (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-05-12). Common (popmax 7.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with thyroid dyshormonogenesis 3.

What condition is associated with TG p.Ile444= (c.1332C>T)?

TG p.Ile444= (c.1332C>T) is associated with thyroid dyshormonogenesis 3 (ClinVar).

How is Familial thyroid dyshormonogenesis inherited?

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

TG p.Ile444=

Q: How common is TG p.Ile444= (c.1332C>T) in the general population?

TG p.Ile444= (c.1332C>T) is common (popmax 7.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1332C>T · rs61741629 · VCV776385

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 7.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

thyroid dyshormonogenesis 3

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 -2.1	GERP -0.85
Overall
CADD	0.494	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.5% African / African-American · 5,626/75,050 alleles

Filtering AF 7.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.27%

Overall 0.394% 6,366/1,614,182 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.5%	13
Remaining individualsnot grpmax-eligible	0.534%	187
Admixed American	0.405%	247
Middle Eastern	0.363%	276
South Asian	0.0165%	6,072
European (non-Finnish)	0.0106%	9,440
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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: TG
Protein: p.Ile444=
Coding: c.1332C>T
MANE Select: NM_003235
dbSNP: rs61741629
Type: single nucleotide variant
Location: chr8:132886704 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 444: 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

For Familial thyroid dyshormonogenesis (Orphanet):

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

Similar variants

TG c.274+2T>G Pathogenic ★★ same condition
TG c.3634+1G>A Likely pathogenic ★★ same condition
TG c.5686+1G>A Pathogenic ★★ same condition
TG c.5686+1G>T Pathogenic ★★ same condition
TG c.638+5G>A Pathogenic/Likely pathogenic ★★ same condition
TG c.6782+1G>T Likely pathogenic ★★ same condition
TG c.7863-1G>A Likely pathogenic ★★ same condition
TG p.Arg1530Ter 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-ile444 (accessed [today's date]).

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