COG2 p.Asn381=
c.1143C>T · rs370937568 · VCV731773
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00314%, 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 1.4 | GERP 1.8, phastCons 0.81 |
| Overall | ||
| CADD | 9.61 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00314%
European (non-Finnish) · 37/1,179,000 alleles
Filtering AF
0.00232%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00202%
Overall
0.00242%
39/1,612,732 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00314% | 31,865 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,416 |
| African / African-American | 0.00134% | 74,886 |
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.Asn381=
- Coding
- c.1143C>T
- MANE Select
- NM_007357
- dbSNP
- rs370937568
- Type
- single nucleotide variant
- Location
- chr1:230679029 (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-asn381 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown