Is TG p.Gln1069Ter (c.3205C>T) pathogenic?

TG p.Gln1069Ter (c.3205C>T) is classified Pathogenic in TG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-04). Very rare (popmax 0.00113%, sas).

How common is TG p.Gln1069Ter (c.3205C>T) in the general population?

TG p.Gln1069Ter (c.3205C>T) is very rare (popmax 0.00113%, sas) (gnomAD).

TG p.Gln1069Ter

c.3205C>T · rs780765199 · VCV2804862

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00113%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 48
Splicing
SpliceAI	Δ0.28	donor loss · deltas
Pangolin	Δ0.46	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.38	GERP -1.4
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00113% South Asian · 1/88,166 alleles

Overall 6.25e-05% 1/1,599,338 alleles · very rare exomes 1/1,447,006 · genomes 0/152,332 · joint denominator

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.Gln1069Ter
Coding: c.3205C>T
MANE Select: NM_003235
dbSNP: rs780765199
Type: single nucleotide variant
Location: chr8:132898234 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Residue 1069: the thyroglobulin type-1 8 domain

Full TG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TG p.Gln1069= Likely benign ★ same residue
TG c.274+1G>A Pathogenic ★★ same type
TG c.274+2T>G Pathogenic ★★ same type
TG c.3634+1G>A Likely pathogenic ★★ same type
TG c.4528+1G>A Pathogenic/Likely pathogenic ★★ same type
TG c.5686+1G>A Pathogenic ★★ same type
TG c.5686+1G>T Pathogenic ★★ same type
TG c.638+5G>A Pathogenic/Likely pathogenic ★★ same type

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-gln1069ter (accessed [today's date]).

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