DIO1 p.Leu13Phe
c.37C>T · VCV4240597
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.197 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.27 | GERP -1.3, phastCons 0.17 |
| Overall | ||
| CADD | 16.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,062 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00718%
Overall
0.00192%
31/1,614,164 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,021 |
| East Asian | 0.0134% | 7,481 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,837 |
| Admixed American | 0.00333% | 30,007 |
| European (non-Finnish) | 0.00144% | 69,413 |
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.Leu13Phe
- Coding
- c.37C>T
- MANE Select
- NM_001193369 · reported on NM_000792
- Type
- single nucleotide variant
- Location
- chr1:53894247 (GRCh38)
- Structure
- AlphaFold pLDDT 46.89 · 2 PDB
- Residue 13
- the 'disordered' region; a UniProt-annotated variant site (in)
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-leu13phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown