EFEMP2 p.Pro330=
c.990G>A · rs61740381 · VCV472834
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.261%, afr)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.83 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.46 | gain · loss 0.20 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -1 | GERP -3.7 |
| Overall | ||
| CADD | 23.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.261%
African / African-American · 196/75,020 alleles
Filtering AF
0.231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.22%
Overall
0.0168%
271/1,613,722 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.261% | 383 |
| Admixed American | 0.0817% | 1,225 |
| Remaining individualsnot grpmax-eligible | 0.0304% | 3,289 |
| Middle Eastern | 0.0165% | 6,046 |
| South Asian | 0.00329% | 30,359 |
| European (non-Finnish) | 0.000254% | 393,309 |
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.Pro330=
- Coding
- c.990G>A
- MANE Select
- NM_016938
- dbSNP
- rs61740381
- Type
- single nucleotide variant
- Location
- chr11:65868041 (GRCh38)
- Gene constraint
- LOEUF 0.56 · pLI 0.62 (gnomAD)
- Structure
- AlphaFold pLDDT 82.95 · 1 PDB
Similar variants
- EFEMP2 p.Pro330Leu Uncertain significance ★★ ⚠ same residue
- EFEMP2 p.Pro330Arg Uncertain significance ★ ⚠ same residue
- EFEMP2 p.Arg279Cys Likely pathogenic ★★ same condition
- EFEMP2 p.Asp203Ala Pathogenic/Likely pathogenic ★★ same condition
- EFEMP2 p.Glu126Lys Pathogenic/Likely pathogenic ★★ same condition
- EFEMP2 p.Glu161Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- EFEMP2 p.Glu167Ter Pathogenic ★★ same condition
- EFEMP2 c.161-6C>G Uncertain significance ★★ same condition
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-pro330 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown