CELSR2 p.Ile2250=
c.6750C>A · rs745890195 · VCV3041783
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000509%, nfe)
Conditions
1
CELSR2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.20 | donor gain, 23 bp away · raw score · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 13.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,179,918 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,612,816 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
- CELSR2
- Protein
- p.Ile2250=
- Coding
- c.6750C>A
- MANE Select
- NM_001408
- dbSNP
- rs745890195
- Type
- single nucleotide variant
- Location
- chr1:109269228 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Residue 2250
- the gain-b domain
Disease context
CELSR2-related disorder
Similar variants
- CELSR2 p.Arg426Ter Uncertain significance same condition
- CELSR2 p.Arg881Ter Uncertain significance same condition
- CELSR2 p.Ala2579= Likely benign same condition
- CELSR2 p.Arg2015= Benign same condition
- CELSR2 p.Arg2191His Likely benign same condition
- CELSR2 p.Asn1182= Likely benign same condition
- CELSR2 p.Asn1830= Likely benign same condition
- CELSR2 p.Gln2053= Likely benign same condition
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/celsr2-p-ile2250 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown