CELSR2 p.Pro2214=
c.6642C>T · rs369285532 · VCV2638974
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0664%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.67 · evaluated, not missing |
|---|---|---|
| Pangolin | Δ0.29 | gain · loss 0.12 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP -16 | GERP -3.2 |
| Overall | ||
| CADD | 1.034 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0664%
Middle Eastern · 4/6,026 alleles
Filtering AF
0.0226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0136%
Overall
0.00993%
159/1,601,132 alleles · ultra-rare
exomes 144/1,448,916 · genomes 15/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0664% | 1,507 |
| European (non-Finnish) | 0.0121% | 8,264 |
| African / African-American | 0.00807% | 12,385 |
| South Asian | 0.00443% | 22,575 |
| Admixed American | 0.00348% | 28,766 |
| Remaining individualsnot grpmax-eligible | 0.00162% | 61,830 |
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.Pro2214=
- Coding
- c.6642C>T
- MANE Select
- NM_001408
- dbSNP
- rs369285532
- Type
- single nucleotide variant
- Location
- chr1:109269120 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Residue 2214
- the gain-b domain; the 'disordered' region
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-pro2214 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown