EGF p.Ser437=
c.1311C>T · VCV3703803
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0362%, 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 -0.87 | GERP -4.1, phastCons 0.014 |
| Overall | ||
| CADD | 7.067 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0362%
South Asian · 33/91,072 alleles
Filtering AF
0.0265%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0231%
Overall
0.00514%
83/1,613,416 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0362% | 2,760 |
| Middle Eastern | 0.0164% | 6,080 |
| Admixed American | 0.015% | 6,663 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,818 |
| European (non-Finnish) | 0.00297% | 33,703 |
| African / African-American | 0.00267% | 37,428 |
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.Ser437=
- Coding
- c.1311C>T
- MANE Select
- NM_001963
- Type
- single nucleotide variant
- Location
- chr4:109961984 (GRCh38)
- Gene constraint
- LOEUF 0.741 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.66 · 13 PDB
- Residue 437
- the egf-like 3 domain; the egf-like 4 domain
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-ser437 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown