CELSR1 p.Ala2547=
c.7641C>T · rs866723729 · VCV2653314
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0495%, mid)
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 1 | GERP -0.84, phastCons 1 |
| Overall | ||
| CADD | 9.187 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0495%
Middle Eastern · 3/6,056 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00719%
Overall
0.000434%
7/1,613,100 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0495% | 2,019 |
| African / African-American | 0.00133% | 75,060 |
| European (non-Finnish) | 0.000254% | 393,275 |
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.Ala2547=
- Coding
- c.7641C>T
- MANE Select
- NM_001378328
- dbSNP
- rs866723729
- Type
- single nucleotide variant
- Location
- chr22:46373001 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI <0.01 (gnomAD)
- Residue 2547
- a UniProt-annotated variant site (in lmphm9)
Similar variants
- CELSR1 p.Ala2547Val Uncertain significance ★ same residue
- 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
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-ala2547 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown