CELSR1 p.Leu425=
c.1275C>G · rs1009154 · VCV1326604
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 97.5%, eas) — too common for a highly-penetrant pathogenic allele
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 0.11 | GERP -0.38, phastCons 0.003 |
| Overall | ||
| CADD | 8.028 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
97.5%
East Asian · 43,503/44,622 alleles
Filtering AF
96.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 96.4%
Overall
93.2%
1,498,771/1,607,706 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 97.5% | 1 |
| Amishnot grpmax-eligible | 96.8% | 1 |
| Admixed American | 96.3% | 1 |
| Finnishnot grpmax-eligible | 94.9% | 1 |
| European (non-Finnish) | 93.3% | 1 |
| Remaining individualsnot grpmax-eligible | 92.9% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 92.6% | 1 |
| South Asian | 91.7% | 1 |
| African / African-American | 89% | 1 |
| Middle Eastern | 85.4% | 1 |
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
- CELSR1
- Protein
- p.Leu425=
- Coding
- c.1275C>G
- MANE Select
- NM_001378328
- dbSNP
- rs1009154
- Type
- single nucleotide variant
- Location
- chr22:46535896 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI <0.01 (gnomAD)
- Residue 425
- a UniProt-annotated variant site (in lmphm9); the cadherin 2 domain
Similar variants
- CELSR1 p.Ala2442Val Uncertain significance ★★ ⚠ same type
- CELSR1 p.Ala2955Thr Uncertain significance ★★ ⚠ same type
- CELSR1 p.Ala396Ser Uncertain significance ★★ ⚠ same type
- CELSR1 p.Ala617Ser Uncertain significance ★★ ⚠ same type
- CELSR1 p.Arg1323Gln Uncertain significance ★★ ⚠ same type
- CELSR1 p.Arg1379His Uncertain significance ★★ ⚠ same type
- CELSR1 p.Arg1643Gln Uncertain significance ★★ ⚠ same type
- CELSR1 p.Arg1720Trp 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/celsr1-p-leu425 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown