TG p.Pro1178=
c.3534A>G · rs150888797 · VCV2898897
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0961%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.006 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -4.4 | GERP -3.1 |
| Overall | ||
| CADD | 0.096 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0961%
African / African-American · 72/74,944 alleles
Filtering AF
0.0782%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0716%
Overall
0.00477%
77/1,614,066 alleles · ultra-rare
exomes 28/1,461,846 · genomes 49/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0961% | 1,041 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,623 |
| Admixed American | 0.00167% | 60,008 |
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.Pro1178=
- Coding
- c.3534A>G
- MANE Select
- NM_003235
- dbSNP
- rs150888797
- Type
- single nucleotide variant
- Location
- chr8:132901453 (GRCh38)
- Gene constraint
- LOEUF 0.892 · pLI <0.01 (gnomAD)
- Residue 1178
- the thyroglobulin type-1 10 domain
Similar variants
- 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
- TG c.6782+1G>T 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-pro1178 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown