Is TG p.Thr607= (c.1821C>T) pathogenic?

TG p.Thr607= (c.1821C>T) is classified Benign/Likely benign in TG (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-31). Common (popmax 6.46%, afr) — too common for a highly-penetrant pathogenic allele; Associated with thyroid dyshormonogenesis 3.

What condition is associated with TG p.Thr607= (c.1821C>T)?

TG p.Thr607= (c.1821C>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.Thr607=

Q: How common is TG p.Thr607= (c.1821C>T) in the general population?

TG p.Thr607= (c.1821C>T) is common (popmax 6.46%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1821C>T · rs61742713 · VCV792111

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.46%, 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 0.091	GERP 0.073, phastCons 0.63
Overall
CADD	7.616	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.46% African / African-American · 4,844/74,932 alleles

Filtering AF 6.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.25%

Overall 0.34% 5,485/1,613,310 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.46%	15
Remaining individualsnot grpmax-eligible	0.439%	228
Admixed American	0.354%	283
Middle Eastern	0.347%	289
South Asian	0.0154%	6,504
European (non-Finnish)	0.0101%	9,912
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,574

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.Thr607=
Coding: c.1821C>T
MANE Select: NM_003235
dbSNP: rs61742713
Type: single nucleotide variant
Location: chr8:132887193 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 607: an α-helix; the thyroglobulin type-1 5 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-thr607 (accessed [today's date]).

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