CPLANE1 p.Ala2725=
c.8175A>C · rs201122718 · VCV261676
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.874%, mid)
Conditions
1
Joubert syndrome 17
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 -1.4 | GERP -3.1 |
| Overall | ||
| CADD | 0.402 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.874%
Middle Eastern · 53/6,062 alleles
Filtering AF
0.687%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.619%
Overall
0.028%
452/1,614,132 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.874% | 114 |
| Ashkenazi Jewishnot grpmax-eligible | 0.534% | 187 |
| Admixed American | 0.0867% | 1,154 |
| Remaining individualsnot grpmax-eligible | 0.0832% | 1,202 |
| African / African-American | 0.0107% | 9,381 |
| European (non-Finnish) | 0.0103% | 9,752 |
| South Asian | 0.00769% | 13,011 |
| Finnishnot grpmax-eligible | 0.00156% | 64,036 |
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
- CPLANE1
- Protein
- p.Ala2725=
- Coding
- c.8175A>C
- MANE Select
- NM_001384732
- dbSNP
- rs201122718
- Type
- single nucleotide variant
- Location
- chr5:37153938 (GRCh38)
- Gene constraint
- LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 2725
- a UniProt-annotated variant site (in ofd6; likely pathogenic)
Similar variants
- CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same condition
- CPLANE1 c.2291+1G>A Likely pathogenic ★★ same condition
- CPLANE1 c.2291+2T>C Pathogenic/Likely pathogenic ★★ same condition
- CPLANE1 c.2292-1G>A Likely pathogenic ★★ same condition
- CPLANE1 c.2500+1G>A Likely pathogenic ★★ same condition
- CPLANE1 c.3290-2A>G Pathogenic/Likely pathogenic ★★ same condition
- CPLANE1 c.3673-1G>C Pathogenic/Likely pathogenic ★★ same condition
- CPLANE1 c.677+1G>C Likely pathogenic ★★ same condition
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/cplane1-p-ala2725 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown