CPLANE1 p.Val1265=
c.3795T>A · rs74478954 · VCV158033
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.84%, afr)
Conditions
1
Joubert syndrome 17
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.25 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -0.79, phastCons 0.99 |
| Overall | ||
| CADD | 5.195 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.84%
African / African-American · 3,619/74,806 alleles
Filtering AF
4.71%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.65%
Overall
0.564%
9,086/1,610,988 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.84% | 21 |
| Middle Eastern | 2.17% | 46 |
| South Asian | 1.01% | 99 |
| Remaining individualsnot grpmax-eligible | 0.687% | 146 |
| Admixed American | 0.581% | 172 |
| European (non-Finnish) | 0.307% | 325 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0475% | 2,107 |
| Finnishnot grpmax-eligible | 0.0141% | 7,109 |
| East Asian | 0.00224% | 44,704 |
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.Val1265=
- Coding
- c.3795T>A
- MANE Select
- NM_001384732
- dbSNP
- rs74478954
- Type
- single nucleotide variant
- Location
- chr5:37195874 (GRCh38)
- Gene constraint
- LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- CPLANE1 p.Val1265Phe Uncertain significance ★ ⚠ same residue
- 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
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-val1265 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown