DIO1 p.Arg241Cys
c.721C>T · rs766339963 · VCV2344104
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0483%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.293 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 2.3, phastCons 1 |
| Overall | ||
| CADD | 26.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0483%
Admixed American · 29/60,018 alleles
Filtering AF
0.0345%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0299%
Overall
0.00294%
43/1,461,862 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0483% | 2,070 |
| South Asian | 0.0022% | 45,540 |
| European (non-Finnish) | 0.00102% | 98,333 |
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.Arg241Cys
- Coding
- c.721C>T
- MANE Select
- NM_001193369 · reported on NM_000792
- dbSNP
- rs766339963
- Type
- single nucleotide variant
- Location
- chr1:53909970 (GRCh38)
- Structure
- AlphaFold pLDDT 46.89 · 2 PDB
- Residue 241
- 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-arg241cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown