A2ML1 p.Arg1001=
c.3003G>A · rs200269317 · VCV515641
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.137%, 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 0.14 | GERP -1.2, phastCons 0.001 |
| Overall | ||
| CADD | 7.119 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.137%
African / African-American · 103/75,016 alleles
Filtering AF
0.116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.108%
Overall
0.00651%
105/1,613,986 alleles · rare
exomes 47/1,461,766 · genomes 58/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.137% | 728 |
| Admixed American | 0.00167% | 59,998 |
| South Asian | 0.0011% | 91,056 |
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
- A2ML1
- Protein
- p.Arg1001=
- Coding
- c.3003G>A
- MANE Select
- NM_144670
- dbSNP
- rs200269317
- Type
- single nucleotide variant
- Location
- chr12:8857318 (GRCh38)
- Gene constraint
- LOEUF 0.953 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.61 · 5 PDB
- Residue 1001
- an α-helix; a UniProt-annotated variant site (risk factor for otitis media); a UniProt-annotated variant site (may be a risk factor for otitis media)
Similar variants
- A2ML1 p.Arg1001Gln Uncertain significance ★★ ⚠ same residue
- A2ML1 p.Arg1001Trp Uncertain significance ★★ ⚠ same residue
- A2ML1 c.1834-1G>T Uncertain significance ★★ same type
- A2ML1 c.3264+4C>T Uncertain significance ★★ same type
- A2ML1 c.3933+4A>G Uncertain significance ★★ same type
- A2ML1 c.409+1G>A Uncertain significance ★★ same type
- A2ML1 c.4221+2T>C Uncertain significance ★★ same type
- A2ML1 c.*1+1G>A 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/a2ml1-p-arg1001 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown