DIO3 p.Asn164Ser
c.491A>G · VCV4011721
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.161 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.25 | constrained · MANE · 39 bp · p 0.00089 · regional, not allelic |
| Overall | ||
| CADD | 24.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,002 alleles
Filtering AF
0.00239%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0021%
Overall
0.00256%
41/1,602,796 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,001 |
| European (non-Finnish) | 0.00322% | 31,052 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,422 |
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.Asn164Ser
- Coding
- c.491A>G
- MANE Select
- NM_001362
- Type
- single nucleotide variant
- Location
- chr14:101561987 (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-asn164ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown