COG2 p.Cys16Ter
c.48C>A · rs2102736333 · VCV1691000
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
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. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 1 of 18 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.9 | GERP 0.82, phastCons 1 |
| Overall | ||
| CADD | 38.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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
- COG2
- Protein
- p.Cys16Ter
- Coding
- c.48C>A
- MANE Select
- NM_007357
- dbSNP
- rs2102736333
- Type
- single nucleotide variant
- Location
- chr1:230642654 (GRCh38)
- Gene constraint
- LOEUF 0.724 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.38
Similar variants
- COG2 p.Ala160Val Uncertain significance ★★ ⚠ same type
- COG2 p.Ala339Pro Uncertain significance ★★ ⚠ same type
- COG2 p.Arg138Gln Uncertain significance ★★ ⚠ same type
- COG2 p.Arg241Gln Uncertain significance ★★ ⚠ same type
- COG2 p.Arg356Gln Uncertain significance ★★ ⚠ same type
- COG2 p.Arg356Trp Uncertain significance ★★ ⚠ same type
- COG2 p.Arg39Gln Uncertain significance ★★ ⚠ same type
- COG2 p.Arg39Trp 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/cog2-p-cys16ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown