COG4 p.Pro673=
c.2019G>A · rs140971621 · VCV507008
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -2.4 | GERP -3.5 |
| Overall | ||
| CADD | 9.957 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,960 alleles
Filtering AF
0.00247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00217%
Overall
0.0031%
50/1,613,540 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,987 |
| African / African-American | 0.004% | 24,975 |
| European (non-Finnish) | 0.00331% | 30,253 |
| South Asian | 0.0033% | 30,333 |
| East Asian | 0.00223% | 44,886 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
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.Pro673=
- Coding
- c.2019G>A
- MANE Select
- NM_015386
- dbSNP
- rs140971621
- Type
- single nucleotide variant
- Location
- chr16:70481851 (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 673
- an α-helix; the 'd domain' region
Similar variants
- COG4 p.Pro673Leu Uncertain significance ★ same residue
- COG4 p.Arg177Ter Pathogenic/Likely pathogenic ★★ same type
- COG4 p.Arg733Trp Pathogenic/Likely pathogenic ★★ same type
- COG4 p.Glu614Ter Pathogenic ★★ same type
- COG4 p.Gly25Ter Pathogenic/Likely pathogenic ★★ same type
- COG4 p.Gly516Arg Pathogenic ★★ same type
- COG4 p.Ala251Thr Uncertain significance ★★ same type
- COG4 p.Ala544Val 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/cog4-p-pro673 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown