EMC1 p.Phe953Ser
c.2858T>C · rs1267383375 · VCV691806
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9997 | likely pathogenic · top 1% in EMC1 |
|---|---|---|
| REVEL | 0.719 | pathogenic-leaning |
| SaProt | LLR -12.27 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.4 | GERP 1, phastCons 1 |
| Regional constraint | o/e 0.82 | unconstrained · MANE · 14 kb · p 4e-06 · regional, not allelic |
| Overall | ||
| CADD | 30.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,854 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,506 |
| European (non-Finnish) | 0.000508% | 196,668 |
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.Phe953Ser
- Coding
- c.2858T>C
- MANE Select
- NM_015047
- dbSNP
- rs1267383375
- Type
- single nucleotide variant
- Location
- chr1:19219427 (GRCh38)
- Gene constraint
- LOEUF 0.913 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.67 · 10 PDB
- Residue 953
- a β-strand
Similar variants
- EMC1 p.Phe953Leu Uncertain significance ★ ⚠ same residue
- EMC1 p.Phe953Tyr Uncertain significance ★ ⚠ same residue
- EMC1 p.Tyr378Ter Pathogenic/Likely pathogenic ★★ same condition
- 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
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-phe953ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown