COG1 p.Leu475=
c.1425C>T · VCV3354734
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
COG1-related disorder
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 -1.2 | GERP -0.088 |
| Overall | ||
| CADD | 6.442 | 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
- COG1
- Protein
- p.Leu475=
- Coding
- c.1425C>T
- MANE Select
- NM_018714
- Type
- single nucleotide variant
- Location
- chr17:73201252 (GRCh38)
- Gene constraint
- LOEUF 0.718 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 77.82
Disease context
COG1-related disorder
Similar variants
- COG1 p.Leu475Val Uncertain significance ★ ⚠ same residue
- COG1 p.Asp825= Likely benign same condition
- COG1 c.1070+5G>A Pathogenic ★★ same type
- COG1 p.Arg336Ter Pathogenic ★★ same type
- COG1 p.Trp476Ter Pathogenic/Likely pathogenic ★★ same type
- COG1 p.Ala143Thr Uncertain significance ★★ ⚠ same type
- COG1 p.Ala209Val Uncertain significance ★★ ⚠ same type
- COG1 p.Ala27Ser Uncertain significance ★★ ⚠ 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/cog1-p-leu475 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown