A2ML1 p.Val903=
c.2709C>T · VCV4635634
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00135%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.27 | GERP -3.6, phastCons 0.99 |
| Overall | ||
| CADD | 8.444 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00135%
African / African-American · 1/74,290 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000188%
3/1,596,316 alleles · very rare
exomes 1/1,444,154 · genomes 2/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00135% | 74,290 |
| European (non-Finnish) | 0.000171% | 585,967 |
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.Val903=
- Coding
- c.2709C>T
- MANE Select
- NM_144670
- Type
- single nucleotide variant
- Location
- chr12:8854246 (GRCh38)
- Gene constraint
- LOEUF 0.953 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.61 · 5 PDB
- Residue 903
- a β-strand; a UniProt-annotated variant site (risk factor for otitis media)
Similar variants
- A2ML1 p.Val903Ile 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
- A2ML1 p.Ala1002Val 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-val903 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown