COBL p.Ala57=
c.171G>A · rs79885281 · VCV722670
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.12%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -3.5 |
| Overall | ||
| CADD | 6.813 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.12%
African / African-American · 838/75,032 alleles
Filtering AF
1.05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.03%
Overall
0.0667%
1,077/1,614,098 alleles · low-frequency
exomes 594/1,461,818 · genomes 483/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.12% | 90 |
| Middle Eastern | 0.198% | 505 |
| Admixed American | 0.0983% | 1,017 |
| Remaining individualsnot grpmax-eligible | 0.0944% | 1,059 |
| South Asian | 0.00988% | 10,120 |
| European (non-Finnish) | 0.00839% | 11,920 |
| Finnishnot grpmax-eligible | 0.00156% | 63,972 |
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
- COBL
- Protein
- p.Ala57=
- Coding
- c.171G>A
- MANE Select
- NM_015198
- dbSNP
- rs79885281
- Type
- single nucleotide variant
- Location
- chr7:51219815 (GRCh38)
- Gene constraint
- LOEUF 0.638 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.88 · 1 PDB
Similar variants
- 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
- COBL p.Ala1130Ser 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/cobl-p-ala57 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown