DIO1 p.Val77Ile
c.229G>A · rs754392287 · VCV3082404
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 6.19e-05%)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.057 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.71 | donor loss, 1 bp away · masked 0 · deltas |
| Constraint at this position | ||
| Conservation | phyloP 8.3 | GERP -0.2, phastCons 1 |
| Overall | ||
| CADD | 21.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.19e-05%
Overall
6.19e-05%
1/1,614,224 alleles · very rare
exomes 1/1,461,894 · genomes 0/152,330 · joint denominator
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.Val77Ile
- Coding
- c.229G>A
- MANE Select
- NM_000792
- dbSNP
- rs754392287
- Type
- single nucleotide variant
- Location
- chr1:53894439 (GRCh38)
- Structure
- AlphaFold pLDDT 46.89 · 2 PDB
- Residue 77
- 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-val77ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown