COG4 p.Leu243Phe
c.727C>T · rs2507536645 · VCV1806816
Uncertain significance
Single submitter
Classification
Uncertain significance
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. | ||
| REVEL | 0.463 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.4 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 1.06 | unconstrained · MANE · 43 kb · p 0.075 · regional, not allelic |
| Overall | ||
| CADD | 28.3 | 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
- COG4
- Protein
- p.Leu243Phe
- Coding
- c.727C>T
- MANE Select
- NM_015386
- dbSNP
- rs2507536645
- Type
- single nucleotide variant
- Location
- chr16:70512250 (GRCh38)
- Gene constraint
- LOEUF 0.805 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.29 · 1 PDB
Similar variants
- COG4 p.Arg177Ter Pathogenic/Likely pathogenic ★★ same type
- COG4 p.Arg733Trp Pathogenic/Likely pathogenic ★★ same type
- COG4 p.Glu614Ter Pathogenic ★★ same type
- COG4 p.Gly25Ter Pathogenic/Likely pathogenic ★★ same type
- COG4 p.Gly516Arg Pathogenic ★★ same type
- COG4 p.Ala251Thr Uncertain significance ★★ same type
- COG4 p.Ala544Val Uncertain significance ★★ same type
- COG4 p.Ala599Thr 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/cog4-p-leu243phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown