CELSR2 c.8338+12C>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.184%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +12 | near-intronic (+12 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.2 | GERP -1.1, phastCons 0.25 |
| Non-coding constraint | Z 3.04 | 1 kb window · o/e 0.75 · regional · uncalibrated |
| Overall | ||
| CADD | 1.187 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.184%
African / African-American · 138/74,888 alleles
Filtering AF
0.159%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.15%
Overall
0.0105%
168/1,605,082 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.184% | 543 |
| Admixed American | 0.0269% | 3,715 |
| Remaining individualsnot grpmax-eligible | 0.00968% | 10,335 |
| European (non-Finnish) | 0.000681% | 146,832 |
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
- Coding
- c.8338+12C>A
- MANE Select
- NM_001408
- Type
- single nucleotide variant
- Location
- chr1:109273039 (GRCh38)
- Gene constraint
- LOEUF 0.396 · pLI 1.00 (gnomAD)
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-c-8338-plus-12c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown