EGFLAM p.Ala585=
c.1755C>T · VCV3843737
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.115%, afr)
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 -12 | GERP -3.7 |
| Overall | ||
| CADD | 4.31 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.115%
African / African-American · 86/74,882 alleles
Filtering AF
0.0952%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.088%
Overall
0.00663%
107/1,613,904 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.115% | 871 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| South Asian | 0.00329% | 30,358 |
| European (non-Finnish) | 0.0011% | 90,769 |
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
- EGFLAM
- Protein
- p.Ala585=
- Coding
- c.1755C>T
- MANE Select
- NM_152403
- Type
- single nucleotide variant
- Location
- chr5:38425037 (GRCh38)
- Gene constraint
- LOEUF 0.83 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.81 · 3 PDB
- Residue 585
- a disulfide bond; the egf-like 2 domain
Similar variants
- EGFLAM p.Asn913= Benign ★★ same type
- EGFLAM p.Trp229Arg Benign ★★ same type
- EGFLAM c.2465-2611T>C Uncertain significance ★ ⚠ same type
- EGFLAM p.Ala115Val Uncertain significance ★ ⚠ same type
- EGFLAM p.Ala143Pro Uncertain significance ★ ⚠ same type
- EGFLAM p.Ala314Thr Uncertain significance ★ ⚠ same type
- EGFLAM p.Ala45Thr Uncertain significance ★ ⚠ same type
- EGFLAM p.Ala515Thr 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/egflam-p-ala585 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown