EGF p.Leu858=
c.2572T>C · VCV4748824
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
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 0.029 | GERP -2.9, phastCons 0.96 |
| Overall | ||
| CADD | 4.489 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,090 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000929%
15/1,613,784 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,218 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,476 |
| European (non-Finnish) | 0.000763% | 131,093 |
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.Leu858=
- Coding
- c.2572T>C
- MANE Select
- NM_001963
- Type
- single nucleotide variant
- Location
- chr4:109987824 (GRCh38)
- Gene constraint
- LOEUF 0.741 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.66 · 13 PDB
- Residue 858
- the egf-like 6 domain; a disulfide bond
Similar variants
- EGF p.Leu858Ter Uncertain significance ★ same residue
- 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
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-leu858 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown