COG6 p.Val576=
c.1728G>A · VCV4919928
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00511%, 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 3.2 | GERP 0.21, phastCons 1 |
| Overall | ||
| CADD | 8.257 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00511%
Admixed American · 3/58,744 alleles
Filtering AF
0.00328%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0029%
Overall
0.00353%
55/1,557,198 alleles · very rare
exomes 49/1,411,782 · genomes 6/145,416 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00511% | 19,581 |
| European (non-Finnish) | 0.00423% | 23,642 |
| African / African-American | 0.00419% | 23,881 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,582 |
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
- COG6
- Protein
- p.Val576=
- Coding
- c.1728G>A
- MANE Select
- NM_020751
- Type
- single nucleotide variant
- Location
- chr13:39724543 (GRCh38)
- Gene constraint
- LOEUF 1.057 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.62
Similar variants
- COG6 c.1166+1G>A Likely pathogenic ★★ same type
- COG6 c.1167-24A>G Pathogenic/Likely pathogenic ★★ same type
- COG6 p.Arg171Ter Pathogenic ★★ same type
- COG6 p.Arg360Ter Pathogenic/Likely pathogenic ★★ same type
- COG6 p.Leu512Ter Pathogenic/Likely pathogenic ★★ same type
- COG6 c.*1532T>G Uncertain significance ★★ same type
- COG6 c.*52G>A Uncertain significance ★★ same type
- COG6 p.Ala13Thr 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/cog6-p-val576 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown