CELSR2 p.Phe1604=
c.4812T>C · rs41309211 · VCV1597905
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 18.7%, afr) — too common for a highly-penetrant pathogenic allele
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 -8.6 | GERP -3.9 |
| Overall | ||
| CADD | 0.247 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
18.7%
African / African-American · 13,874/74,370 alleles
Filtering AF
18.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 18.3%
Overall
1.02%
16,194/1,585,088 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 18.7% | 5 |
| Remaining individualsnot grpmax-eligible | 1.33% | 75 |
| Middle Eastern | 1.22% | 82 |
| Admixed American | 1.12% | 89 |
| European (non-Finnish) | 0.0637% | 1,569 |
| South Asian | 0.0345% | 2,901 |
| Finnishnot grpmax-eligible | 0.00317% | 31,501 |
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.Phe1604=
- Coding
- c.4812T>C
- MANE Select
- NM_001408
- dbSNP
- rs41309211
- Type
- single nucleotide variant
- Location
- chr1:109263245 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
- Residue 1604
- the egf-like 4; calcium-binding domain; a disulfide bond
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-phe1604 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown