COG5 p.Leu216=
c.646C>T · rs1584789628 · VCV760739
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 0.43 | GERP -1.6, phastCons 0.017 |
| Overall | ||
| CADD | 4.684 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- COG5
- Protein
- p.Leu216=
- Coding
- c.646C>T
- MANE Select
- NM_006348
- dbSNP
- rs1584789628
- Type
- single nucleotide variant
- Location
- chr7:107412525 (GRCh38)
- Gene constraint
- LOEUF 1.026 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37
Similar variants
- COG5 p.Leu216Val Uncertain significance ★ ⚠ same residue
- GPR22 p.Gln216Arg Uncertain significance ★ ⚠ same residue
- COG5 c.1475+1G>A Likely pathogenic ★★ same type
- COG5 c.2295+2T>C Pathogenic/Likely pathogenic ★★ same type
- COG5 p.Arg205Ter Pathogenic ★★ same type
- COG5 p.Arg283Ter Pathogenic ★★ same type
- COG5 p.Arg461Ter Pathogenic/Likely pathogenic ★★ same type
- COG5 p.Arg690Ter 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/cog5-p-leu216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown