Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 60.6%, mid) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +252 | deep intronic (+252 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP -2.3 |
| Non-coding constraint | Z 1.89 | 1 kb window · o/e 0.83 · regional · uncalibrated |
| Overall | ||
| CADD | 6.132 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
60.6%
Middle Eastern · 1,193/1,968 alleles
Filtering AF
57.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 56.6%
Overall
48.6%
265,469/545,910 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 60.6% | 2 |
| South Asian | 56.6% | 2 |
| Finnishnot grpmax-eligible | 56.3% | 2 |
| European (non-Finnish) | 51.3% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 48.7% | 2 |
| Remaining individualsnot grpmax-eligible | 48.6% | 2 |
| African / African-American | 45.2% | 2 |
| Amishnot grpmax-eligible | 42% | 2 |
| Admixed American | 35.8% | 3 |
| East Asian | 19.9% | 5 |
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
- Coding
- c.727+252A>G
- MANE Select
- NM_016938
- dbSNP
- rs570387
- Type
- single nucleotide variant
- Location
- chr11:65869605 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.62 (gnomAD)
- Structure
- AlphaFold pLDDT 82.95 · 1 PDB
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-c-727-plus-252a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown