CPLANE1 p.Pro2986=
c.8958A>G · rs138495618 · VCV640502
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0659%, mid)
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 -1.6 | GERP -0.59 |
| Overall | ||
| CADD | 6.471 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0659%
Middle Eastern · 4/6,072 alleles
Filtering AF
0.0224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.0112%
181/1,610,286 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0659% | 1,518 |
| Ashkenazi Jewishnot grpmax-eligible | 0.044% | 2,271 |
| Admixed American | 0.0169% | 5,900 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,928 |
| European (non-Finnish) | 0.0121% | 8,243 |
| African / African-American | 0.00134% | 74,660 |
| South Asian | 0.00111% | 90,290 |
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.Pro2986=
- Coding
- c.8958A>G
- MANE Select
- NM_001384732
- dbSNP
- rs138495618
- Type
- single nucleotide variant
- Location
- chr5:37125244 (GRCh38)
- Gene constraint
- LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 2986
- a UniProt-annotated variant site (in ofd6; likely pathogenic); the 'disordered' region
Similar variants
- CPLANE1 p.Pro2986Leu Uncertain significance ★★ ⚠ same residue
- CPLANE1 c.1372-2A>G Pathogenic/Likely pathogenic ★★ same type
- CPLANE1 c.2291+1G>A Likely pathogenic ★★ same type
- CPLANE1 c.2291+2T>C Pathogenic/Likely pathogenic ★★ same type
- CPLANE1 c.2292-1G>A Likely pathogenic ★★ same type
- CPLANE1 c.2500+1G>A Likely pathogenic ★★ same type
- CPLANE1 c.2920+1G>A Likely pathogenic ★★ same type
- CPLANE1 c.3290-2A>G Pathogenic/Likely pathogenic ★★ 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/cplane1-p-pro2986 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown