EIF2B2 p.Pro311fs
c.932_933del · rs1160961207 · VCV2875995
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 34.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.0109% | 9,144 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish)grpmax | 0.000424% | 235,999 |
Finnish 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
- EIF2B2
- Protein
- p.Pro311fs
- Coding
- c.932_933del
- MANE Select
- NM_014239
- dbSNP
- rs1160961207
- Type
- Deletion
- Location
- chr14:75009064 (GRCh38)
- Gene constraint
- LOEUF 1.25 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.82 · 38 PDB
Disease context
leukoencephalopathy with vanishing white matter — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor CACH syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood
Similar variants
- EIF2B2 p.Ile190fs Pathogenic/Likely pathogenic ★★ same condition
- EIF2B2 p.Ile15fs Pathogenic ★ same condition
- EIF2B2 p.Pro311= Likely benign ★ same residue
- EIF2B2 c.285-1G>A Likely pathogenic ★★ same condition
- EIF2B2 p.Glu213Gly Pathogenic ★★ ⚠ same condition
- EIF2B2 p.Glu304Ter Pathogenic/Likely pathogenic ★★ same condition
- EIF2B2 p.Gly200Val Pathogenic/Likely pathogenic ★★ same condition
- EIF2B2 p.Lys273Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
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/eif2b2-p-pro311fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown