EML1 p.Pro577=
c.1731C>T · rs371443414 · VCV2918422
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00687%, nfe)
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 -7.6 | GERP -3.5 |
| Overall | ||
| CADD | 4.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00687%
European (non-Finnish) · 81/1,178,780 alleles
Filtering AF
0.00563%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00515%
Overall
0.00554%
89/1,607,722 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00687% | 14,553 |
| Remaining individualsnot grpmax-eligible | 0.00482% | 20,763 |
| Admixed American | 0.00346% | 28,869 |
| East Asian | 0.00223% | 44,828 |
| Finnishnot grpmax-eligible | 0.00156% | 63,952 |
| African / African-American | 0.00134% | 74,520 |
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
- EML1
- Protein
- p.Pro577=
- Coding
- c.1731C>T
- MANE Select
- NM_004434
- dbSNP
- rs371443414
- Type
- single nucleotide variant
- Location
- chr14:99914676 (GRCh38)
- Gene constraint
- LOEUF 0.36 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 86.49 · 1 PDB
- Residue 577
- the 'tandem atypical propeller in emls' region; a UniProt-annotated variant site (in bh); a β-strand
Similar variants
- EML1 p.Ala292Val Uncertain significance ★★ ⚠ same type
- EML1 p.Arg192His Uncertain significance ★★ ⚠ same type
- EML1 p.Arg450Gln Uncertain significance ★★ ⚠ same type
- EML1 p.Arg813His Uncertain significance ★★ ⚠ same type
- EML1 p.Cys369Phe Uncertain significance ★★ ⚠ same type
- EML1 p.Gln409Glu Uncertain significance ★★ ⚠ same type
- EML1 p.His351Gln Uncertain significance ★★ ⚠ same type
- EML1 p.Val253Met 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/eml1-p-pro577 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown