CELSR2 p.Leu25=
c.75G>A · rs577620209 · VCV2896925
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.075%, amr)
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 0.39 | GERP 0.55 |
| Overall | ||
| CADD | 3.465 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.075%
Admixed American · 43/57,370 alleles
Filtering AF
0.0572%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0509%
Overall
0.00282%
45/1,596,632 alleles · ultra-rare
exomes 27/1,444,368 · genomes 18/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.075% | 1,334 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,612 |
| European (non-Finnish) | 8.52e-05% | 1,173,476 |
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.Leu25=
- Coding
- c.75G>A
- MANE Select
- NM_001408
- dbSNP
- rs577620209
- Type
- single nucleotide variant
- Location
- chr1:109250154 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
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-leu25 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown