Is TG p.Asp340= (c.1020C>T) pathogenic?

TG p.Asp340= (c.1020C>T) is classified Conflicting classifications of pathogenicity in TG (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0208%, nfe); Associated with thyroid dyshormonogenesis 3.

What condition is associated with TG p.Asp340= (c.1020C>T)?

TG p.Asp340= (c.1020C>T) is associated with thyroid dyshormonogenesis 3, autoimmune thyroid disease, susceptibility to, 3 (ClinVar).

How common is TG p.Asp340= (c.1020C>T) in the general population?

TG p.Asp340= (c.1020C>T) is ultra-rare (popmax 0.0208%, nfe) (gnomAD).

How is Familial thyroid dyshormonogenesis inherited?

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

TG p.Asp340=

c.1020C>T · rs138114586 · VCV909064

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, nfe)

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 -14	GERP -4.1
Overall
CADD	1.597	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0208% European (non-Finnish) · 246/1,179,988 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.0164% 264/1,613,970 alleles · ultra-rare exomes 234/1,461,818 · genomes 30/152,152 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0219%	4,573
European (non-Finnish)grpmax	0.0208%	4,797
Admixed American	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0032%	31,243

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp340=
Coding: c.1020C>T
MANE Select: NM_003235
dbSNP: rs138114586
Type: single nucleotide variant
Location: chr8:132882944 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 340: the thyroglobulin type-1 4 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

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 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-asp340 (accessed [today's date]).

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