EMC1 p.Ser357=
c.1071G>A · rs143891566 · VCV724128
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.297%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.039 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.24 | acceptor loss, 41 bp away · masked 0 · deltas |
| Pangolin | Δ0.26 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -7 | GERP -4.5 |
| Overall | ||
| CADD | 5.262 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.297%
Middle Eastern · 18/6,060 alleles
Filtering AF
0.192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.159%
Overall
0.0221%
356/1,611,416 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.297% | 337 |
| Ashkenazi Jewishnot grpmax-eligible | 0.28% | 357 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,837 |
| South Asian | 0.0187% | 5,353 |
| European (non-Finnish) | 0.0175% | 5,717 |
| Admixed American | 0.0117% | 8,572 |
| African / African-American | 0.00267% | 37,460 |
| Finnishnot grpmax-eligible | 0.00156% | 64,028 |
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
- EMC1
- Protein
- p.Ser357=
- Coding
- c.1071G>A
- MANE Select
- NM_015047
- dbSNP
- rs143891566
- Type
- single nucleotide variant
- Location
- chr1:19238813 (GRCh38)
- Gene constraint
- LOEUF 0.913 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.67 · 10 PDB
- Residue 357
- a β-strand; a disulfide bond
Similar variants
- EMC1 p.Ser357Leu Uncertain significance ★★ ⚠ same residue
- EMC1 c.287-1G>A Likely pathogenic ★★ same type
- EMC1 c.787-1G>A Likely pathogenic ★★ same type
- EMC1 p.Arg105Ter Pathogenic/Likely pathogenic ★★ same type
- EMC1 p.Arg660Ter Pathogenic/Likely pathogenic ★★ same type
- EMC1 p.Arg687Ter Pathogenic/Likely pathogenic ★★ same type
- EMC1 p.Arg69Ter Pathogenic/Likely pathogenic ★★ same type
- EMC1 p.Arg908Ter Pathogenic ★★ 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/emc1-p-ser357 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown