CELSR1 p.Ala2419=
c.7257C>T · VCV3490039
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, 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 0.016 | GERP 0.063 |
| Overall | ||
| CADD | 6.136 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/59,958 alleles
Filtering AF
0.00662%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00592%
Overall
0.00645%
104/1,611,966 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,495 |
| European (non-Finnish) | 0.00772% | 12,960 |
| African / African-American | 0.004% | 24,978 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,376 |
| South Asian | 0.0011% | 90,884 |
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.Ala2419=
- Coding
- c.7257C>T
- MANE Select
- NM_001378328
- Type
- single nucleotide variant
- Location
- chr22:46378717 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI <0.01 (gnomAD)
- Residue 2419
- a disulfide bond; a UniProt-annotated variant site (in lmphm9); the gain-b domain; the 'gps' region
Similar variants
- CELSR1 p.Ala2419Val 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-ala2419 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown