DIO3 p.Ser252=
c.756G>T · VCV3770502
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.311%, nfe)
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 -3.5 | GERP -3.6 |
| Overall | ||
| CADD | 1.398 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.311%
European (non-Finnish) · 3,669/1,180,038 alleles
Filtering AF
0.303%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.299%
Overall
0.244%
3,936/1,612,726 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.311% | 322 |
| Remaining individualsnot grpmax-eligible | 0.224% | 446 |
| Admixed American | 0.09% | 1,112 |
| African / African-American | 0.0613% | 1,632 |
| Finnishnot grpmax-eligible | 0.0272% | 3,680 |
| South Asian | 0.00878% | 11,386 |
| East Asian | 0.00446% | 22,442 |
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
- DIO3
- Protein
- p.Ser252=
- Coding
- c.756G>T
- MANE Select
- NM_001362
- Type
- single nucleotide variant
- Location
- chr14:101562252 (GRCh38)
- Gene constraint
- LOEUF 0.537 · pLI 0.95 (gnomAD)
Similar variants
- DIO3 p.Ala155Val Uncertain significance ★ same type
- DIO3 p.Ala20Thr Uncertain significance ★ same type
- DIO3 p.Ala240Thr Uncertain significance ★ same type
- DIO3 p.Ala40Gly Uncertain significance ★ same type
- DIO3 p.Ala40Val Uncertain significance ★ same type
- DIO3 p.Arg291Ser Uncertain significance ★ same type
- DIO3 p.Arg300Trp Uncertain significance ★ same type
- DIO3 p.Arg75Cys 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/dio3-p-ser252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown