Is TG p.Ser179= (c.537A>G) pathogenic?

TG p.Ser179= (c.537A>G) is classified Conflicting classifications of pathogenicity in TG (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.641%, afr); Associated with thyroid dyshormonogenesis 3.

What condition is associated with TG p.Ser179= (c.537A>G)?

TG p.Ser179= (c.537A>G) is associated with thyroid dyshormonogenesis 3 (ClinVar).

How common is TG p.Ser179= (c.537A>G) in the general population?

TG p.Ser179= (c.537A>G) is rare (popmax 0.641%, afr) (gnomAD).

How is Familial thyroid dyshormonogenesis inherited?

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

TG p.Ser179=

c.537A>G · rs114875802 · VCV785265

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.641%, afr)

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	0.062	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.641% African / African-American · 481/75,030 alleles

Filtering AF 0.594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.575%

Overall 0.0375% 605/1,614,140 alleles · rare exomes 321/1,461,856 · genomes 284/152,284 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.641%	156
Remaining individualsnot grpmax-eligible	0.0816%	1,226
Admixed American	0.065%	1,539
Middle Eastern	0.033%	3,030
European (non-Finnish)	0.00263%	38,065
South Asian	0.0011%	91,068

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.Ser179=
Coding: c.537A>G
MANE Select: NM_003235
dbSNP: rs114875802
Type: single nucleotide variant
Location: chr8:132873120 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 179: the thyroglobulin type-1 3 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-ser179 (accessed [today's date]).

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