CELSR1 p.Asp1874=
c.5622C>T · rs34107040 · VCV714909
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.86%, 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 1.9 | GERP 0.64, phastCons 1 |
| Overall | ||
| CADD | 5.414 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.86%
African / African-American · 2,129/74,562 alleles
Filtering AF
2.75%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.71%
Overall
0.153%
2,456/1,600,478 alleles · low-frequency
exomes 1,191/1,448,264 · genomes 1,265/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.86% | 35 |
| Remaining individualsnot grpmax-eligible | 0.262% | 382 |
| Admixed American | 0.221% | 452 |
| Middle Eastern | 0.0995% | 1,005 |
| South Asian | 0.0135% | 7,381 |
| East Asian | 0.00228% | 43,940 |
| European (non-Finnish) | 0.00136% | 73,315 |
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.Asp1874=
- Coding
- c.5622C>T
- MANE Select
- NM_001378328
- dbSNP
- rs34107040
- Type
- single nucleotide variant
- Location
- chr22:46397753 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI <0.01 (gnomAD)
- Residue 1874
- a UniProt-annotated variant site (in lmphm9); the egf-like 5; calcium-binding domain
Similar variants
- CELSR1 p.Asp1874Gly 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-asp1874 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown