DIO3 p.Ser7Pro
c.19T>C · rs1030878626 · VCV2304690
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00017%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.034 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.6 | GERP 0.14, phastCons 1 |
| Regional constraint | o/e 0.90 | unconstrained · MANE · 473 bp · p 0.13 · regional, not allelic |
| Overall | ||
| CADD | 18.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00017%
European (non-Finnish) · 2/1,176,064 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000138%
2/1,454,130 alleles · very rare
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.Ser7Pro
- Coding
- c.19T>C
- MANE Select
- NM_001362
- dbSNP
- rs1030878626
- Type
- single nucleotide variant
- Location
- chr14:101561515 (GRCh38)
- Gene constraint
- LOEUF 0.537 · pLI 0.95 (gnomAD)
- Residue 7
- the 'disordered' region
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-ser7pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown