COG8 p.Ser355=
c.1065C>G · VCV3257228
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
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 1.7 | GERP -3.6, phastCons 1 |
| Overall | ||
| CADD | 6.669 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,092 alleles
Overall
0.000657%
1/152,198 alleles · very rare
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
- COG8
- Protein
- p.Ser355=
- Coding
- c.1065C>G
- MANE Select
- NM_032382
- Type
- single nucleotide variant
- Location
- chr16:69334869 (GRCh38)
- Gene constraint
- LOEUF 1.257 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.67
Similar variants
- COG8 c.1583-1G>A Pathogenic/Likely pathogenic ★★ same type
- COG8 p.Ala16Gly Uncertain significance ★★ ⚠ same type
- COG8 p.Ala2Val Uncertain significance ★★ ⚠ same type
- COG8 p.Ala458Val Uncertain significance ★★ ⚠ same type
- COG8 p.Ala5Val Uncertain significance ★★ ⚠ same type
- COG8 p.Arg102Cys Uncertain significance ★★ ⚠ same type
- COG8 p.Arg140Gln Uncertain significance ★★ ⚠ same type
- COG8 p.Arg244Lys 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/cog8-p-ser355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown