EGF p.Leu2=
c.6G>A · rs758291999 · VCV3008136
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.01%, 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 4.2 | GERP 0.83, phastCons 1 |
| Overall | ||
| CADD | 4.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.01%
Admixed American · 6/59,984 alleles
Filtering AF
0.00428%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00295%
Overall
0.000411%
6/1,461,444 alleles · ultra-rare
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
- EGF
- Protein
- p.Leu2=
- Coding
- c.6G>A
- MANE Select
- NM_001963
- dbSNP
- rs758291999
- Type
- single nucleotide variant
- Location
- chr4:109913341 (GRCh38)
- Gene constraint
- LOEUF 0.741 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.66 · 13 PDB
Similar variants
- EGF c.2221+4C>T Uncertain significance ★★ same type
- EGF c.2858-11G>T Uncertain significance ★★ same type
- EGF c.-60C>T Uncertain significance ★★ same type
- EGF p.Ala1025Ser Uncertain significance ★★ ⚠ same type
- EGF p.Ala1037Val Uncertain significance ★★ ⚠ same type
- EGF p.Ala45Val Uncertain significance ★★ ⚠ same type
- EGF p.Ala862Thr Uncertain significance ★★ ⚠ same type
- EGF p.Arg213Gln 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/egf-p-leu2 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown