EFEMP2 p.Cys188=
c.564C>T · VCV3767605
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.36 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.86 | GERP -3.7 |
| Overall | ||
| CADD | 16.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,082 alleles
Filtering AF
0.00223%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00198%
Overall
0.00248%
40/1,613,720 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,361 |
| European (non-Finnish) | 0.00305% | 32,779 |
| East Asian | 0.00223% | 44,900 |
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
- EFEMP2
- Protein
- p.Cys188=
- Coding
- c.564C>T
- MANE Select
- NM_016938
- Type
- single nucleotide variant
- Location
- chr11:65870164 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.62 (gnomAD)
- Structure
- AlphaFold pLDDT 82.95 · 1 PDB
- Residue 188
- a disulfide bond; the egf-like 3; calcium-binding domain
Similar variants
- EFEMP2 p.Arg279Cys Likely pathogenic ★★ same type
- EFEMP2 p.Arg337Ter Pathogenic/Likely pathogenic ★★ same type
- EFEMP2 p.Asp203Ala Pathogenic/Likely pathogenic ★★ same type
- EFEMP2 p.Glu126Lys Pathogenic/Likely pathogenic ★★ same type
- EFEMP2 p.Glu161Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
- EFEMP2 p.Glu167Ter Pathogenic ★★ same type
- EFEMP2 c.161-6C>G Uncertain significance ★★ same type
- EFEMP2 c.491-5C>G 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/efemp2-p-cys188 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown