COG2 c.72+67G>C
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 94.3%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +67 | deep intronic (+67 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.82 | GERP -2.5 |
| Non-coding constraint | Z 2.09 | 1 kb window · o/e 0.83 · regional · uncalibrated |
| Overall | ||
| CADD | 4.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
94.3%
East Asian · 37,569/39,822 alleles
Filtering AF
93.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 93.2%
Overall
69%
1,026,300/1,487,484 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 94.3% | 1 |
| Admixed American | 82.1% | 1 |
| South Asian | 81% | 1 |
| African / African-American | 80.9% | 1 |
| Remaining individualsnot grpmax-eligible | 70.4% | 1 |
| Amishnot grpmax-eligible | 69.6% | 1 |
| Middle Eastern | 68.4% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 68.3% | 1 |
| European (non-Finnish) | 66% | 2 |
| Finnishnot grpmax-eligible | 64.1% | 2 |
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
- Coding
- c.72+67G>C
- MANE Select
- NM_007357
- dbSNP
- rs4846864
- Type
- single nucleotide variant
- Location
- chr1:230642745 (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-c-72-plus-67g-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown