EFEMP1 p.Ser402=
c.1206T>C · rs991475191 · VCV1626894
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0307%, afr)
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 -0.53 | GERP -5.2 |
| Overall | ||
| CADD | 5.479 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0307%
African / African-American · 23/74,920 alleles
Filtering AF
0.021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0178%
Overall
0.00167%
27/1,613,712 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0307% | 3,257 |
| South Asian | 0.0022% | 45,536 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| European (non-Finnish) | 8.48e-05% | 1,179,856 |
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.Ser402=
- Coding
- c.1206T>C
- MANE Select
- NM_001039348
- dbSNP
- rs991475191
- Type
- single nucleotide variant
- Location
- chr2:55870834 (GRCh38)
- Gene constraint
- LOEUF 0.373 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.67
- Residue 402
- a UniProt-annotated variant site (in arcl1d; likely pathogenic); the 'mediates interaction with timp3' region
Similar variants
- EFEMP1 p.Ser402Thr Uncertain significance ★ ⚠ same residue
- 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
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-ser402 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown