EMC1 p.Ile759=
c.2277C>T · rs710871 · VCV1170556
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 12.4%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.57 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.6 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 9.187 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
12.4%
African / African-American · 9,264/74,980 alleles
Filtering AF
12.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 12.1%
Overall
0.74%
11,942/1,614,108 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 12.4% | 8 |
| South Asian | 1.4% | 71 |
| Remaining individualsnot grpmax-eligible | 1% | 100 |
| Middle Eastern | 0.874% | 114 |
| Admixed American | 0.833% | 120 |
| European (non-Finnish) | 0.0188% | 5,315 |
| East Asian | 0.00223% | 44,880 |
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.Ile759=
- Coding
- c.2277C>T
- MANE Select
- NM_015047
- dbSNP
- rs710871
- Type
- single nucleotide variant
- Location
- chr1:19223495 (GRCh38)
- Gene constraint
- LOEUF 0.913 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.67 · 10 PDB
- Residue 759
- a β-strand
Similar variants
- EMC1 p.Ile759Leu 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-ile759 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown