A2M p.Arg586=
c.1756C>A · VCV4915606
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
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 1.2 | GERP -0.15, phastCons 0.003 |
| Overall | ||
| CADD | 1.747 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,862 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.000548%
8/1,460,102 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,409 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,454 |
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
- A2M
- Protein
- p.Arg586=
- Coding
- c.1756C>A
- MANE Select
- NM_000014
- Type
- single nucleotide variant
- Location
- chr12:9098702 (GRCh38)
- Gene constraint
- LOEUF 0.765 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.61 · 13 PDB
Similar variants
- A2M p.Arg586Gly Uncertain significance ★ ⚠ same residue
- A2M p.Arg586Gln Likely benign same residue
- A2M c.3756+4G>A Benign/Likely benign ★★ same type
- A2M p.Ala844= Benign ★★ same type
- A2M p.Asp277Asn Benign ★★ same type
- A2M p.Ile1000Val Benign ★★ same type
- A2M p.Pro261Leu Benign ★★ ⚠ same type
- A2M p.Tyr1152= Benign/Likely 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/a2m-p-arg586 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown