Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 6.32%, afr) — too common for a highly-penetrant pathogenic allele
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 -1.5 | GERP 0.56 |
| Overall | ||
| CADD | 0.798 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.32%
African / African-American · 4,742/75,014 alleles
Filtering AF
6.17%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.11%
Overall
0.335%
5,402/1,613,950 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.32% | 16 |
| Admixed American | 0.505% | 198 |
| Remaining individualsnot grpmax-eligible | 0.407% | 246 |
| Middle Eastern | 0.182% | 551 |
| South Asian | 0.0187% | 5,357 |
| European (non-Finnish) | 0.00636% | 15,732 |
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.Val437=
- Coding
- c.1311G>A
- MANE Select
- NM_000014
- dbSNP
- rs226396
- Type
- single nucleotide variant
- Location
- chr12:9101630 (GRCh38)
- Gene constraint
- LOEUF 0.765 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.61 · 13 PDB
Similar variants
- 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
- A2M p.Val129= 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-val437 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown