TG p.Pro761=
c.2283A>C · rs754741790 · VCV2887527
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00186%, nfe)
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 -4.4 |
| Overall | ||
| CADD | 0.012 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00186%
European (non-Finnish) · 22/1,180,004 alleles
Filtering AF
0.00122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00143%
23/1,613,860 alleles · very rare
exomes 18/1,461,882 · genomes 5/151,978 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00186% | 53,637 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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.Pro761=
- Coding
- c.2283A>C
- MANE Select
- NM_003235
- dbSNP
- rs754741790
- Type
- single nucleotide variant
- Location
- chr8:132888090 (GRCh38)
- Gene constraint
- LOEUF 0.892 · pLI <0.01 (gnomAD)
- Residue 761
- 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-pro761 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown