CELSR2 p.Ser517=
c.1551T>C · rs454107 · VCV1608258
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 100%, 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 -5.4 | GERP -4 |
| Overall | ||
| CADD | 1.972 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
100%
East Asian · 44,837/44,856 alleles
Filtering AF
99.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 98.9%
Overall
95.4%
1,539,286/1,613,832 alleles · common
exomes 1,401,517/1,461,788 · genomes 137,769/152,044 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 100% | 1 |
| European (non-Finnish) | 96.5% | 1 |
| Admixed American | 96.3% | 1 |
| Finnishnot grpmax-eligible | 95.2% | 1 |
| Middle Eastern | 95.1% | 1 |
| Remaining individualsnot grpmax-eligible | 94.8% | 1 |
| South Asian | 94.6% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 93.3% | 1 |
| Amishnot grpmax-eligible | 90.9% | 1 |
| African / African-American | 76% | 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
- CELSR2
- Protein
- p.Ser517=
- Coding
- c.1551T>C
- MANE Select
- NM_001408
- dbSNP
- rs454107
- Type
- single nucleotide variant
- Location
- chr1:109251630 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Residue 517
- 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-ser517 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown