TG p.Pro840=
c.2520T>C · rs116489694 · VCV778402
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.74%, afr)
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 -0.48 | GERP -4, phastCons 0.098 |
| Overall | ||
| CADD | 3.004 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.74%
African / African-American · 1,303/74,992 alleles
Filtering AF
1.66%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.63%
Overall
0.107%
1,730/1,614,110 alleles · low-frequency
exomes 966/1,461,894 · genomes 764/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.74% | 58 |
| Middle Eastern | 0.214% | 466 |
| Remaining individualsnot grpmax-eligible | 0.179% | 558 |
| Admixed American | 0.178% | 561 |
| European (non-Finnish) | 0.0162% | 6,178 |
| South Asian | 0.00439% | 22,771 |
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.Pro840=
- Coding
- c.2520T>C
- MANE Select
- NM_003235
- dbSNP
- rs116489694
- Type
- single nucleotide variant
- Location
- chr8:132888327 (GRCh38)
- Gene constraint
- LOEUF 0.892 · pLI <0.01 (gnomAD)
- Residue 840
- the thyroglobulin type-1 7 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-pro840 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown