Is TG p.Asp142= (c.426C>T) pathogenic?

TG p.Asp142= (c.426C>T) is classified Conflicting classifications of pathogenicity in TG (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.44%, eas); Associated with thyroid dyshormonogenesis 3.

What condition is associated with TG p.Asp142= (c.426C>T)?

TG p.Asp142= (c.426C>T) is associated with thyroid dyshormonogenesis 3 (ClinVar).

How common is TG p.Asp142= (c.426C>T) in the general population?

TG p.Asp142= (c.426C>T) is low-frequency (popmax 1.44%, eas) (gnomAD).

How is Familial thyroid dyshormonogenesis inherited?

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

TG p.Asp142=

c.426C>T · rs114477962 · VCV735018

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.44%, eas)

Conditions

thyroid dyshormonogenesis 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.4	GERP -3.3
Overall
CADD	8.529	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.44% East Asian · 644/44,868 alleles

Filtering AF 1.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.31%

Overall 0.0636% 1,026/1,614,070 alleles · low-frequency exomes 823/1,461,890 · genomes 203/152,180 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.44%	70
Ashkenazi Jewishnot grpmax-eligible	0.399%	251
African / African-American	0.168%	595
Remaining individualsnot grpmax-eligible	0.104%	962
South Asian	0.0275%	3,643
Middle Eastern	0.0165%	6,062
Admixed American	0.0133%	7,501
European (non-Finnish)	0.00331%	30,257

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.Asp142=
Coding: c.426C>T
MANE Select: NM_003235
dbSNP: rs114477962
Type: single nucleotide variant
Location: chr8:132871499 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 142: the thyroglobulin type-1 2 domain

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-asp142 (accessed [today's date]).

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