MPEG1 p.Trp630Arg
c.1888T>C · VCV3397615
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9728 | likely pathogenic · top 1% in MPEG1 |
|---|---|---|
| REVEL | 0.634 | indeterminate |
| SaProt | LLR -14.74 | damaging |
| ⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 1.00 | unconstrained · MANE · 2,147 bp · p 0.89 · regional, not allelic |
| Overall | ||
| CADD | 25.3 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,926 |
| European (non-Finnish)grpmax | 0.00373% | 26,818 |
| Admixed American | 0.00167% | 59,992 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- MPEG1
- Protein
- p.Trp630Arg
- Coding
- c.1888T>C
- MANE Select
- NM_001039396
- Type
- single nucleotide variant
- Location
- chr11:59210978 (GRCh38)
- Gene constraint
- LOEUF 1.941 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 83.22 · 5 PDB
- Residue 630
- a UniProt-annotated variant site (in imd77; decreased defense response to bacterium); the 'p2' region; a β-strand
Similar variants
- MPEG1 p.Ala525Val Uncertain significance ★★ ⚠ same type
- MPEG1 p.Gln259Glu Uncertain significance ★★ ⚠ same type
- MPEG1 p.Gln713Arg Uncertain significance ★★ ⚠ same type
- MPEG1 p.His420Tyr Uncertain significance ★★ ⚠ same type
- MPEG1 p.Ala467= Benign ★★ same type
- MPEG1 p.Thr73Ala Likely benign ★★ same type
- MPEG1 p.Ala238Thr Uncertain significance ★ ⚠ same type
- MPEG1 p.Ala238Val Uncertain significance ★ ⚠ 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/mpeg1-p-trp630arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown