DIO1 p.Pro96=
c.288G>A · rs35678003 · VCV708355
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.07%, 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 -15 | GERP -3.5 |
| Overall | ||
| CADD | 0.619 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.07%
African / African-American · 2,304/75,020 alleles
Filtering AF
2.97%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.92%
Overall
0.157%
2,534/1,614,150 alleles · low-frequency
exomes 1,202/1,461,882 · genomes 1,332/152,268 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.07% | 33 |
| Remaining individualsnot grpmax-eligible | 0.198% | 504 |
| Middle Eastern | 0.165% | 606 |
| Admixed American | 0.13% | 769 |
| South Asian | 0.00329% | 30,356 |
| European (non-Finnish) | 0.00127% | 78,670 |
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.Pro96=
- Coding
- c.288G>A
- MANE Select
- NM_000792
- dbSNP
- rs35678003
- Type
- single nucleotide variant
- Location
- chr1:53894498 (GRCh38)
- Gene constraint
- LOEUF 0.924 · pLI <0.01 (gnomAD)
Similar variants
- DIO1 p.Arg12Gly Uncertain significance ★ same type
- DIO1 p.Arg241Cys Uncertain significance ★ same type
- DIO1 p.Arg78Cys Uncertain significance ★ same type
- DIO1 p.Asn167Lys Uncertain significance ★ same type
- DIO1 p.Glu239Lys Uncertain significance ★ same type
- DIO1 p.Glu46Lys Uncertain significance ★ same type
- DIO1 p.Gly222Ser Uncertain significance ★ same type
- DIO1 p.Gly45Cys 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/dio1-p-pro96 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown