DIO2 p.Arg144Cys
c.430C>T · VCV3502004
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.174 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.049 | GERP -4.3, phastCons 0.77 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 8,780 bp · p 0.049 · regional, not allelic |
| Overall | ||
| CADD | 19.41 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,870 alleles
Filtering AF
0.000689%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000539%
Overall
0.00105%
17/1,613,892 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,870 |
| Admixed American | 0.00167% | 60,018 |
| African / African-American | 0.00133% | 75,026 |
| European (non-Finnish) | 0.00119% | 84,276 |
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
- DIO2
- Protein
- p.Arg144Cys
- Coding
- c.430C>T
- MANE Select
- NM_013989
- Type
- single nucleotide variant
- Location
- chr14:80203081 (GRCh38)
- Gene constraint
- LOEUF 1.286 · pLI <0.01 (gnomAD)
Similar variants
- DIO2 p.Arg144His Uncertain significance ★ same residue
- DIO2 p.Val89= Benign ★★ same type
- DIO2 p.Arg214Leu Uncertain significance ★ same type
- DIO2 p.Arg255Trp Uncertain significance ★ same type
- DIO2 p.Arg61His Uncertain significance ★ same type
- DIO2 p.Asn100Ser Uncertain significance ★ same type
- DIO2 p.Gln207Glu Uncertain significance ★ same type
- DIO2 p.Glu149Ala Uncertain significance ★ 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/dio2-p-arg144cys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown