CPLANE1 p.Val1416=
c.4248G>A · rs758567108 · VCV905350
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 0.0164%, mid)
Conditions
2
Joubert syndrome 17
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.51 | GERP -3.4 |
| Overall | ||
| CADD | 4.498 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.00105%
17/1,613,956 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| African / African-American | 0.004% | 24,977 |
| Finnishnot grpmax-eligible | 0.00156% | 64,022 |
| European (non-Finnish) | 0.00102% | 98,331 |
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.Val1416=
- Coding
- c.4248G>A
- MANE Select
- NM_001384732
- dbSNP
- rs758567108
- Type
- single nucleotide variant
- Location
- chr5:37185021 (GRCh38)
- Gene constraint
- LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Similar variants
- CPLANE1 p.Val1416Ala Uncertain significance ★ ⚠ same residue
- CPLANE1 p.Val1416Met Conflicting classifications of pathogenicity ★ ⚠ 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
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-val1416 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown