EFEMP1 p.Cys318=
c.954T>C · rs148177279 · VCV1566451
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, amr)
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 1.1 | GERP -3, phastCons 0.99 |
| Overall | ||
| CADD | 7.039 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
Admixed American · 8/59,746 alleles
Filtering AF
0.00664%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00484%
Overall
0.00304%
49/1,609,848 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0134% | 7,468 |
| European (non-Finnish) | 0.00331% | 30,195 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,117 |
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
- EFEMP1
- Protein
- p.Cys318=
- Coding
- c.954T>C
- MANE Select
- NM_001039348
- dbSNP
- rs148177279
- Type
- single nucleotide variant
- Location
- chr2:55874992 (GRCh38)
- Gene constraint
- LOEUF 0.373 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.67
- Residue 318
- a disulfide bond; a UniProt-annotated variant site (in arcl1d; likely pathogenic); the egf-like 5; calcium-binding domain; the 'mediates interaction with timp3' region
Similar variants
- EFEMP1 p.Arg345Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- EFEMP1 p.Ala104Thr Uncertain significance ★★ ⚠ same type
- EFEMP1 p.Ala126Pro Uncertain significance ★★ ⚠ same type
- EFEMP1 p.Ala126Thr Uncertain significance ★★ ⚠ same type
- EFEMP1 p.Ala447Ser Uncertain significance ★★ ⚠ same type
- EFEMP1 p.Ala447Thr Uncertain significance ★★ ⚠ same type
- EFEMP1 p.Arg148His Uncertain significance ★★ ⚠ same type
- EFEMP1 p.Arg156Cys 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/efemp1-p-cys318 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown