DIO1 p.Thr48Met
c.143C>T · rs375309412 · VCV3082403
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0305%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.145 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP 0.41, phastCons 0.99 |
| Overall | ||
| CADD | 22.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0305%
European (non-Finnish) · 360/1,180,042 alleles
Filtering AF
0.0279%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0268%
Overall
0.0232%
375/1,614,090 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0305% | 3,278 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,249 |
| African / African-American | 0.00667% | 14,986 |
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
- DIO1
- Protein
- p.Thr48Met
- Coding
- c.143C>T
- MANE Select
- NM_001193369 · reported on NM_000792
- dbSNP
- rs375309412
- Type
- single nucleotide variant
- Location
- chr1:53894353 (GRCh38)
- Structure
- AlphaFold pLDDT 46.89 · 2 PDB
- Residue 48
- the 'disordered' region
Similar variants
- DIDO1 p.Asp1443= Benign ★★ same type
- DIDO1 p.Glu1498Ala Likely benign ★★ same type
- DIDO1 p.Glu1630Lys Benign ★★ same type
- DIDO1 p.Leu1706Val Benign ★★ same type
- DIDO1 p.Pro136= Benign ★★ same type
- DIDO1 p.Pro616Leu Likely benign ★★ same type
- DIDO1 p.Ser537= Benign ★★ same type
- DIDO1 p.Ser877= Benign ★★ 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/dio1-p-thr48met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown