COG2 p.Leu214=
c.642C>T · VCV4534162
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00458%, nfe)
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 -1.1 | GERP -0.77 |
| Overall | ||
| CADD | 2.157 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00458%
European (non-Finnish) · 54/1,179,876 alleles
Filtering AF
0.00358%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00321%
Overall
0.00359%
58/1,613,872 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00458% | 21,850 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
| African / African-American | 0.00133% | 74,910 |
| South Asian | 0.0011% | 91,080 |
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
- COG2
- Protein
- p.Leu214=
- Coding
- c.642C>T
- MANE Select
- NM_007357
- Type
- single nucleotide variant
- Location
- chr1:230669403 (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-leu214 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown