COG2 p.Pro413=
c.1239G>A · rs541228707 · VCV740649
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.187%, sas)
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 · G>T here scores Δ0.28 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -5.6 |
| Overall | ||
| CADD | 8.477 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.187%
South Asian · 170/91,048 alleles
Filtering AF
0.164%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.155%
Overall
0.0113%
182/1,614,034 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.187% | 536 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| European (non-Finnish) | 0.000339% | 294,998 |
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.Pro413=
- Coding
- c.1239G>A
- MANE Select
- NM_007357
- dbSNP
- rs541228707
- Type
- single nucleotide variant
- Location
- chr1:230685095 (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-pro413 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown