EFCAB2 p.Glu4Lys
c.10G>A · VCV3506869
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.17 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 117 kb · p 0.7 · regional, not allelic |
| Overall | ||
| CADD | 19.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
Admixed American · 9/51,198 alleles
Filtering AF
0.00914%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00676%
Overall
0.00104%
16/1,537,490 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0176% | 5,689 |
| African / African-American | 0.00552% | 18,101 |
| East Asian | 0.00247% | 40,464 |
| European (non-Finnish) | 0.000174% | 574,472 |
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
- EFCAB2
- Protein
- p.Glu4Lys
- Coding
- c.10G>A
- MANE Select
- NM_032328
- Type
- single nucleotide variant
- Location
- chr1:244970428 (GRCh38)
- Gene constraint
- LOEUF 1.466 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.45 · 1 PDB
- Residue 4
- the 'disordered' region
Similar variants
- DRC8 p.Phe73= Benign ★★ same type
- DRC8 p.Ala13Thr Uncertain significance ★ ⚠ same type
- DRC8 p.Asp152Val Uncertain significance ★ same type
- DRC8 p.Asp6Asn Uncertain significance ★ same type
- DRC8 p.Asp6Tyr Uncertain significance ★ ⚠ same type
- DRC8 p.Ile141Thr Uncertain significance ★ same type
- DRC8 p.Val36Leu Uncertain significance ★ ⚠ same type
- EFCAB2 p.Glu116Lys 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/efcab2-p-glu4lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown