DIO2 p.Val89=
c.267C>G · rs143144220 · VCV787950
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.57%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.8 | GERP 1.3, phastCons 1 |
| Overall | ||
| CADD | 4.923 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.57%
African / African-American · 1,155/73,500 alleles
Filtering AF
1.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.47%
Overall
0.0845%
1,356/1,604,534 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.57% | 64 |
| Middle Eastern | 0.215% | 465 |
| Remaining individualsnot grpmax-eligible | 0.116% | 865 |
| Admixed American | 0.0902% | 1,109 |
| South Asian | 0.01% | 9,975 |
| European (non-Finnish) | 0.00459% | 21,785 |
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.Val89=
- Coding
- c.267C>G
- MANE Select
- NM_013989
- dbSNP
- rs143144220
- Type
- single nucleotide variant
- Location
- chr14:80203244 (GRCh38)
- Gene constraint
- LOEUF 1.286 · pLI <0.01 (gnomAD)
Similar variants
- DIO2 p.Arg144Cys Uncertain significance ★ same type
- DIO2 p.Arg144His Uncertain significance ★ 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-val89 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown