COG8 p.Phe269Ile
c.805T>A · VCV3911178
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.0669 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0669 | likely benign |
|---|---|---|
| REVEL | 0.167 | moderately benign-leaning |
| SaProt | LLR -3.25 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.5, phastCons 1 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 8,710 bp · p 0.33 · regional, not allelic |
| Overall | ||
| CADD | 22.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- COG8
- Protein
- p.Phe269Ile
- Coding
- c.805T>A
- MANE Select
- NM_032382
- Type
- single nucleotide variant
- Location
- chr16:69335129 (GRCh38)
- Gene constraint
- LOEUF 1.257 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.67
Similar variants
- COG8 c.1583-1G>A Pathogenic/Likely pathogenic ★★ same type
- COG8 p.Ala16Gly Uncertain significance ★★ ⚠ same type
- COG8 p.Ala2Val Uncertain significance ★★ ⚠ same type
- COG8 p.Ala458Val Uncertain significance ★★ ⚠ same type
- COG8 p.Ala5Val Uncertain significance ★★ ⚠ same type
- COG8 p.Arg102Cys Uncertain significance ★★ ⚠ same type
- COG8 p.Arg140Gln Uncertain significance ★★ ⚠ same type
- COG8 p.Arg244Lys 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/cog8-p-phe269ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown