TG p.Ser814=
c.2442C>T · rs776488821 · VCV2658830
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
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 -7.9 | GERP -4.4 |
| Overall | ||
| CADD | 4.252 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/60,006 alleles
Filtering AF
0.00543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0038%
Overall
0.0026%
42/1,614,090 alleles · ultra-rare
exomes 40/1,461,894 · genomes 2/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,572 |
| East Asian | 0.00445% | 22,450 |
| European (non-Finnish) | 0.00263% | 38,066 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| South Asian | 0.0011% | 91,086 |
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.Ser814=
- Coding
- c.2442C>T
- MANE Select
- NM_003235
- dbSNP
- rs776488821
- Type
- single nucleotide variant
- Location
- chr8:132888249 (GRCh38)
- Gene constraint
- LOEUF 0.892 · pLI <0.01 (gnomAD)
- Residue 814
- 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-ser814 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown