CELSR2 p.Leu540=
c.1620G>A · rs112857965 · VCV1602486
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.43%, afr)
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 0.51 | GERP -1.2, phastCons 0.99 |
| Overall | ||
| CADD | 3.264 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.43%
African / African-American · 1,072/74,992 alleles
Filtering AF
1.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.33%
Overall
0.0734%
1,184/1,614,082 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.43% | 70 |
| Remaining individualsnot grpmax-eligible | 0.0864% | 1,158 |
| Admixed American | 0.0633% | 1,580 |
| Middle Eastern | 0.033% | 3,031 |
| South Asian | 0.0022% | 45,542 |
| European (non-Finnish) | 0.00136% | 73,751 |
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.Leu540=
- Coding
- c.1620G>A
- MANE Select
- NM_001408
- dbSNP
- rs112857965
- Type
- single nucleotide variant
- Location
- chr1:109251699 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Residue 540
- the cadherin 4 domain
Similar variants
- CELSR2 c.8338+1G>C Uncertain significance ★★ same type
- CELSR2 p.Ala1114Val Uncertain significance ★★ ⚠ same type
- CELSR2 p.Ala2145Thr Uncertain significance ★★ ⚠ same type
- CELSR2 p.Ala2574Thr Uncertain significance ★★ ⚠ same type
- CELSR2 p.Arg1171Gln Uncertain significance ★★ ⚠ same type
- CELSR2 p.Arg1328His Uncertain significance ★★ ⚠ same type
- CELSR2 p.Arg1400His Uncertain significance ★★ same type
- CELSR2 p.Arg1978Gln 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/celsr2-p-leu540 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown