EMC1 p.Ser747Arg
c.2241C>G · VCV3646128
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.985 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.985 | likely pathogenic · top 8% in EMC1 |
|---|---|---|
| REVEL | 0.226 | benign-leaning |
| SaProt | LLR -15.56 | damaging |
| ⇒ AlphaMissense and SaProt call this damaging; REVEL does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.6 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 0.82 | unconstrained · MANE · 14 kb · p 4e-06 · regional, not allelic |
| Overall | ||
| CADD | 23.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- EMC1
- Protein
- p.Ser747Arg
- Coding
- c.2241C>G
- MANE Select
- NM_015047
- Type
- single nucleotide variant
- Location
- chr1:19223531 (GRCh38)
- Gene constraint
- LOEUF 0.913 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.67 · 10 PDB
- Residue 747
- a β-strand
Similar variants
- EMC1 p.Ser747Asn Uncertain significance ★ ⚠ same residue
- EMC1 p.Ser747fs Pathogenic/Likely pathogenic ★★ 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
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-ser747arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown