A2ML1 p.Val562=
c.1686T>G · rs12296765 · VCV241886
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.74%, 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 -0.38 | GERP -3.6, phastCons 0.44 |
| Overall | ||
| CADD | 0.818 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.74%
African / African-American · 2,792/74,702 alleles
Filtering AF
3.62%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.57%
Overall
0.193%
3,105/1,607,200 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.74% | 27 |
| Admixed American | 0.222% | 450 |
| Middle Eastern | 0.218% | 459 |
| Remaining individualsnot grpmax-eligible | 0.18% | 555 |
| South Asian | 0.0178% | 5,620 |
| European (non-Finnish) | 0.00348% | 28,717 |
| East Asian | 0.00224% | 44,626 |
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.Val562=
- Coding
- c.1686T>G
- MANE Select
- NM_144670
- dbSNP
- rs12296765
- Type
- single nucleotide variant
- Location
- chr12:8847551 (GRCh38)
- Gene constraint
- LOEUF 0.953 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.61 · 5 PDB
- Residue 562
- a UniProt-annotated variant site (risk factor for otitis media)
Similar variants
- A2ML1 p.Val562Leu Uncertain significance ★ ⚠ same residue
- A2ML1 p.Val562Phe 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-val562 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown