CELSR2 p.Thr1126=
c.3378C>T · rs684138 · VCV1540563
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 27.8%, afr) — 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 -0.38 | GERP -4.2, phastCons 0.004 |
| Overall | ||
| CADD | 6.027 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
27.8%
African / African-American · 20,802/74,694 alleles
Filtering AF
27.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 27.4%
Overall
9.97%
159,676/1,601,166 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 27.8% | 4 |
| Amishnot grpmax-eligible | 27.3% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 11.1% | 9 |
| Remaining individualsnot grpmax-eligible | 10.2% | 10 |
| European (non-Finnish) | 9.9% | 10 |
| Finnishnot grpmax-eligible | 9.7% | 10 |
| Middle Eastern | 8.82% | 11 |
| Admixed American | 6.73% | 15 |
| South Asian | 2.65% | 38 |
| East Asian | 0.0158% | 6,328 |
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.Thr1126=
- Coding
- c.3378C>T
- MANE Select
- NM_001408
- dbSNP
- rs684138
- Type
- single nucleotide variant
- Location
- chr1:109258499 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Residue 1126
- the cadherin 9 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-thr1126 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown