COG4 p.Ile620Val
c.1858A>G · rs1377561023 · VCV2225317
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.02 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.42 | GERP -1.9, phastCons 0.99 |
| Regional constraint | o/e 1.06 | unconstrained · MANE · 43 kb · p 0.075 · regional, not allelic |
| Overall | ||
| CADD | 12.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/59,992 alleles
Filtering AF
0.00122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00178%
26/1,461,702 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 29,996 |
| European (non-Finnish) | 0.00186% | 53,632 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,500 |
| African / African-American | 0.00133% | 74,968 |
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
- COG4
- Protein
- p.Ile620Val
- Coding
- c.1858A>G
- MANE Select
- NM_015386
- dbSNP
- rs1377561023
- Type
- single nucleotide variant
- Location
- chr16:70482791 (GRCh38)
- Gene constraint
- LOEUF 0.805 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.29 · 1 PDB
- Residue 620
- an α-helix; the 'd domain' region
Similar variants
- COG4 p.Ala251Thr Uncertain significance ★★ same condition
- COG4 p.Ala544Val Uncertain significance ★★ same condition
- COG4 p.Ala599Thr Uncertain significance ★★ same condition
- COG4 p.Arg177Gln Uncertain significance ★★ same condition
- COG4 p.Arg198His Uncertain significance ★★ same condition
- COG4 p.Arg266Gln Uncertain significance ★★ same condition
- COG4 p.Arg702Gln Uncertain significance ★★ same condition
- COG4 p.Arg763His Uncertain significance ★★ same condition
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/cog4-p-ile620val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown