EML2 p.Ala544=
c.1632G>A · rs750362474 · VCV2650119
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0667%, amr)
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 -10 | GERP -3.8 |
| Overall | ||
| CADD | 0.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0667%
Admixed American · 40/59,984 alleles
Filtering AF
0.0503%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0446%
Overall
0.0039%
63/1,613,926 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0667% | 1,500 |
| African / African-American | 0.00534% | 18,726 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| South Asian | 0.00329% | 30,361 |
| European (non-Finnish) | 0.0011% | 90,765 |
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
- EML2
- Protein
- p.Ala544=
- Coding
- c.1632G>A
- MANE Select
- NM_012155
- dbSNP
- rs750362474
- Type
- single nucleotide variant
- Location
- chr19:45614666 (GRCh38)
- Gene constraint
- LOEUF 0.845 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.78 · 1 PDB
- Residue 544
- the 'tandem atypical propeller in emls' region
Similar variants
- EML2 p.Ala121Val Uncertain significance ★ ⚠ same type
- EML2 p.Ala207Ser Uncertain significance ★ ⚠ same type
- EML2 p.Ala288Val Uncertain significance ★ ⚠ same type
- EML2 p.Ala302Thr Uncertain significance ★ ⚠ same type
- EML2 p.Ala384Val Uncertain significance ★ ⚠ same type
- EML2 p.Ala473Pro Uncertain significance ★ ⚠ same type
- EML2 p.Ala546Thr Uncertain significance ★ ⚠ same type
- EML2 p.Ala571Val 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/eml2-p-ala544 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown