GLIS3 p.Arg503=
c.1509C>T · rs141125402 · VCV1165997
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.348%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -3.4, phastCons 1 |
| Overall | ||
| CADD | 5.403 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.348%
African / African-American · 261/75,064 alleles
Filtering AF
0.313%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.3%
Overall
0.0202%
326/1,613,714 alleles · rare
exomes 170/1,461,386 · genomes 156/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.348% | 288 |
| Middle Eastern | 0.0495% | 2,021 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,718 |
| Admixed American | 0.0283% | 3,531 |
| South Asian | 0.0022% | 45,542 |
| European (non-Finnish) | 0.00169% | 58,999 |
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
- GLIS3
- Protein
- p.Arg503=
- Coding
- c.1509C>T
- MANE Select
- NM_001042413
- dbSNP
- rs141125402
- Type
- single nucleotide variant
- Location
- chr9:4117969 (GRCh38)
- Gene constraint
- LOEUF 0.853 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 49.95
- Residue 503
- the 'disordered' region
Similar variants
- GLIS3 p.Arg503Cys Uncertain significance ★ same residue
- GLIS3 c.596+6A>C Uncertain significance ★★ same type
- GLIS3 c.*3330G>A Uncertain significance ★★ same type
- GLIS3 c.*3344T>A Uncertain significance ★★ same type
- GLIS3 c.*3920G>A Uncertain significance ★★ same type
- GLIS3 c.*69T>C Uncertain significance ★★ same type
- GLIS3 p.Ala233Thr Uncertain significance ★★ ⚠ same type
- GLIS3 p.Ala446Val 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/glis3-p-arg503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown