DIO1 p.Met201Ile
c.603G>A · rs201420507 · VCV1686839
Pathogenic
No assertion criteria
Classification
Pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.59%, sas)
Conditions
1
thyroid hormone metabolism, abnormal, 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.436 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.2, phastCons 1 |
| Overall | ||
| CADD | 27.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.59%
South Asian · 1,445/91,086 alleles
Filtering AF
1.52%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.49%
Overall
0.0945%
1,526/1,614,226 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.59% | 63 |
| Remaining individualsnot grpmax-eligible | 0.0832% | 1,202 |
| Middle Eastern | 0.033% | 3,029 |
| African / African-American | 0.00533% | 18,767 |
| Admixed American | 0.005% | 20,011 |
| East Asian | 0.00223% | 44,890 |
| European (non-Finnish) | 0.00161% | 62,107 |
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.Met201Ile
- Coding
- c.603G>A
- MANE Select
- NM_001193369 · reported on NM_000792
- dbSNP
- rs201420507
- Type
- single nucleotide variant
- Location
- chr1:53906216 (GRCh38)
- Structure
- AlphaFold pLDDT 46.89 · 2 PDB
- Residue 201
- the 'disordered' region
Similar variants
- DIDO1 p.Val201Met Uncertain significance ★ ⚠ same residue
- DIO1 p.Asn94Lys Pathogenic same condition
- 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
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-met201ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown