COBL p.Pro339Arg
c.1016C>G · VCV4004789
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4014 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4014 | ambiguous |
|---|---|---|
| REVEL | 0.331 | indeterminate |
| SaProt | LLR -11.01 | damaging |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.5, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 119 kb · p 0.54 · regional, not allelic |
| Overall | ||
| CADD | 25.8 | 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
- COBL
- Protein
- p.Pro339Arg
- Coding
- c.1016C>G
- MANE Select
- NM_015198
- Type
- single nucleotide variant
- Location
- chr7:51085246 (GRCh38)
- Gene constraint
- LOEUF 0.638 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.88 · 1 PDB
- Residue 339
- the 'disordered' region
Similar variants
- COBL p.Ala57= Benign ★★ same type
- COBL p.Ala655Pro Benign ★★ same type
- COBL p.Gly534Ser Likely benign ★★ same type
- COBL p.His601Tyr Benign ★★ same type
- COBL p.Ser47= Benign ★★ same type
- COBL p.Ser513Phe Benign ★★ same type
- COBL p.Thr1234= Benign ★★ same type
- COBL p.Tyr222= Benign ★★ 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/cobl-p-pro339arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown