CELSR1 p.Ala2996=
c.8988C>G · rs77489567 · VCV720966
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.9%, afr)
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 5.5 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 8.94 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.9%
African / African-American · 2,174/74,994 alleles
Filtering AF
2.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.76%
Overall
0.193%
3,118/1,611,740 alleles · low-frequency
exomes 1,867/1,459,444 · genomes 1,251/152,296 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.9% | 34 |
| South Asian | 0.682% | 147 |
| Middle Eastern | 0.333% | 301 |
| Remaining individualsnot grpmax-eligible | 0.223% | 449 |
| Admixed American | 0.165% | 605 |
| European (non-Finnish) | 0.00534% | 18,721 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,562 |
| East Asian | 0.00223% | 44,838 |
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.Ala2996=
- Coding
- c.8988C>G
- MANE Select
- NM_001378328
- dbSNP
- rs77489567
- Type
- single nucleotide variant
- Location
- chr22:46364043 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI <0.01 (gnomAD)
- Residue 2996
- a UniProt-annotated variant site (in lmphm9); the 'disordered' region
Similar variants
- 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
- CELSR1 p.Arg1720Trp 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-ala2996 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown