A2M p.Ala615=
c.1845G>A · VCV4915604
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.08%, afr)
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 -20 | GERP -8.3 |
| Overall | ||
| CADD | 0.033 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.08%
African / African-American · 805/74,790 alleles
Filtering AF
1.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.99%
Overall
0.0628%
1,004/1,599,906 alleles · low-frequency
exomes 542/1,447,656 · genomes 462/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.08% | 93 |
| Middle Eastern | 0.106% | 940 |
| Remaining individualsnot grpmax-eligible | 0.0983% | 1,018 |
| Admixed American | 0.0847% | 1,181 |
| East Asian | 0.045% | 2,223 |
| South Asian | 0.00793% | 12,605 |
| European (non-Finnish) | 0.00477% | 20,957 |
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.Ala615=
- Coding
- c.1845G>A
- MANE Select
- NM_000014
- Type
- single nucleotide variant
- Location
- chr12:9098613 (GRCh38)
- Gene constraint
- LOEUF 0.765 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.61 · 13 PDB
Similar variants
- A2M p.Ala615Val Uncertain significance ★ ⚠ 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
- A2M p.Val120= 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-ala615 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown