EFEMP1 p.Thr99=
c.297C>T · rs142637468 · VCV726660
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.215%, 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 -4.5 | GERP -4.8 |
| Overall | ||
| CADD | 1.503 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.215%
Admixed American · 129/60,028 alleles
Filtering AF
0.185%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.173%
Overall
0.0367%
593/1,614,212 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.215% | 465 |
| African / African-American | 0.152% | 658 |
| Ashkenazi Jewishnot grpmax-eligible | 0.118% | 846 |
| Remaining individualsnot grpmax-eligible | 0.064% | 1,563 |
| Middle Eastern | 0.033% | 3,029 |
| European (non-Finnish) | 0.0231% | 4,323 |
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.Thr99=
- Coding
- c.297C>T
- MANE Select
- NM_001039348
- dbSNP
- rs142637468
- Type
- single nucleotide variant
- Location
- chr2:55917885 (GRCh38)
- Gene constraint
- LOEUF 0.373 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.67
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-thr99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown