EMC1 p.Ile73Phe
c.217A>T · VCV3369516
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.3691 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.3691 | ambiguous |
|---|---|---|
| REVEL | 0.143 | moderately benign-leaning |
| SaProt | LLR -9.21 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>C here scores Δ0.84 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 16 kb · p 0.24 · regional, not allelic |
| Overall | ||
| CADD | 23.1 | 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.Ile73Phe
- Coding
- c.217A>T
- MANE Select
- NM_015047
- Type
- single nucleotide variant
- Location
- chr1:19244909 (GRCh38)
- Gene constraint
- LOEUF 0.913 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.67 · 10 PDB
- Residue 73
- a β-strand
Similar variants
- EMC1 p.Ile73Met Uncertain significance ★ ⚠ same residue
- EMC1 p.Ile73Val 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
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-ile73phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown