COG1 p.Asp825=
c.2475C>T · rs533834836 · VCV3047686
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0111%, eas)
Conditions
1
COG1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.44 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.51 | GERP -3.5, phastCons 0.001 |
| Overall | ||
| CADD | 6.237 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0111%
East Asian · 5/44,890 alleles
Filtering AF
0.00434%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00276%
Overall
0.00161%
26/1,613,814 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0111% | 8,978 |
| African / African-American | 0.00801% | 12,482 |
| South Asian | 0.00329% | 30,359 |
| European (non-Finnish) | 0.00102% | 98,330 |
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
- COG1
- Protein
- p.Asp825=
- Coding
- c.2475C>T
- MANE Select
- NM_018714
- dbSNP
- rs533834836
- Type
- single nucleotide variant
- Location
- chr17:73205645 (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.Leu475= 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
- COG1 p.Ala380Val 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-asp825 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown