EFEMP1 p.Ser261=
c.783C>T · rs776487850 · VCV1157091
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00187%, nfe)
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 5.9 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 11.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00187%
European (non-Finnish) · 22/1,176,698 alleles
Filtering AF
0.00122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00143%
23/1,608,220 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00187% | 53,486 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,190 |
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.Ser261=
- Coding
- c.783C>T
- MANE Select
- NM_001039348
- dbSNP
- rs776487850
- Type
- single nucleotide variant
- Location
- chr2:55876720 (GRCh38)
- Gene constraint
- LOEUF 0.373 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.67
- Residue 261
- a disulfide bond; a UniProt-annotated variant site (in arcl1d; likely pathogenic); the egf-like 4; 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-ser261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown