TG p.Phe1058=
c.3174C>T · rs140301550 · VCV1677046
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0454%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.024 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -2.6 |
| Overall | ||
| CADD | 0.838 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0454%
African / African-American · 34/74,868 alleles
Filtering AF
0.0334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0292%
Overall
0.0028%
45/1,605,576 alleles · ultra-rare
exomes 23/1,453,526 · genomes 22/152,050 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0454% | 2,202 |
| Middle Eastern | 0.0191% | 5,224 |
| Admixed American | 0.00843% | 11,862 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,726 |
| South Asian | 0.00112% | 88,962 |
| European (non-Finnish) | 8.5e-05% | 1,176,280 |
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.Phe1058=
- Coding
- c.3174C>T
- MANE Select
- NM_003235
- dbSNP
- rs140301550
- Type
- single nucleotide variant
- Location
- chr8:132898203 (GRCh38)
- Gene constraint
- LOEUF 0.892 · pLI <0.01 (gnomAD)
- Residue 1058
- the thyroglobulin type-1 8 domain
Similar variants
- TG p.Phe1058Tyr Uncertain significance ★ ⚠ 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-phe1058 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown