GLIS3 p.Phe274=
c.822T>C · rs750596069 · VCV746014
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
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 -1.4 | GERP -4.3 |
| Overall | ||
| CADD | 1.214 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,012 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,146 alleles · very rare
exomes 2/1,461,888 · genomes 0/152,258 · joint denominator
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.Phe274=
- Coding
- c.822T>C
- MANE Select
- NM_001042413
- dbSNP
- rs750596069
- Type
- single nucleotide variant
- Location
- chr9:4118656 (GRCh38)
- Gene constraint
- LOEUF 0.853 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 49.95
Similar variants
- 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
- GLIS3 p.Ala615Ser 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-phe274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown