FOXE1 p.Arg189=
c.567C>G · VCV4533667
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.241%, sas)
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 -0.09 | GERP -4, phastCons 0.001 |
| Overall | ||
| CADD | 6.411 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.241%
South Asian · 60/24,930 alleles
Filtering AF
0.192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.174%
Overall
0.0114%
140/1,226,388 alleles · rare
exomes 124/1,076,030 · genomes 16/150,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.241% | 415 |
| Middle Eastern | 0.0632% | 1,583 |
| Remaining individualsnot grpmax-eligible | 0.0202% | 4,961 |
| European (non-Finnish) | 0.00679% | 14,724 |
| East Asian | 0.00332% | 30,108 |
| African / African-American | 0.00158% | 63,366 |
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
- FOXE1
- Protein
- p.Arg189=
- Coding
- c.567C>G
- MANE Select
- NM_004473
- Type
- single nucleotide variant
- Location
- chr9:97854481 (GRCh38)
- Gene constraint
- LOEUF 1.926 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 62.02
Similar variants
- FOXE1 p.Ala118Val Uncertain significance ★★ ⚠ same type
- FOXE1 p.Ala206Thr Uncertain significance ★★ ⚠ same type
- FOXE1 p.Arg51Gly Uncertain significance ★★ ⚠ same type
- FOXE1 p.Gly334Ala Uncertain significance ★★ ⚠ same type
- FOXE1 p.Leu205Val Uncertain significance ★★ ⚠ same type
- FOXE1 p.Ser294Asn Uncertain significance ★★ ⚠ same type
- FOXE1 c.-131G>C Benign ★★ same type
- FOXE1 c.-156T>C Benign ★★ 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/foxe1-p-arg189 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown