Is EIF2B4 p.Glu10= (c.30G>A) pathogenic?

EIF2B4 p.Glu10= (c.30G>A) is classified Uncertain significance in EIF2B4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). Very rare (popmax 0.00252%, nfe).

How common is EIF2B4 p.Glu10= (c.30G>A) in the general population?

EIF2B4 p.Glu10= (c.30G>A) is very rare (popmax 0.00252%, nfe) (gnomAD).

EIF2B4 p.Glu10=

c.30G>A · rs759657701 · VCV1935920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00252%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	donor loss, 29 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.9	GERP -0.44, phastCons 1
Overall
CADD	11.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00252% European (non-Finnish) · 29/1,149,484 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00153%

Overall 0.00691% 107/1,548,546 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.14%	717
Remaining individualsnot grpmax-eligible	0.0083%	12,046
European (non-Finnish)grpmax	0.00252%	39,637

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: EIF2B4
Protein: p.Glu10=
Coding: c.30G>A
MANE Select: NM_001034116
dbSNP: rs759657701
Type: single nucleotide variant
Location: chr2:27370285 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.37 · 38 PDB
Residue 10: the 'disordered' region

Full EIF2B4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF2B4 p.Glu10Gln Uncertain significance ★ ⚠ same residue
EIF2B4 c.32-1G>T Likely pathogenic ★★ same type
EIF2B4 p.Arg357Gln Likely pathogenic ★★ ⚠ same type
EIF2B4 p.Pro243Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
EIF2B4 p.Thr502Met Likely pathogenic ★★ same type
EIF2B4 p.Tyr489His Pathogenic/Likely pathogenic ★★ same type
EIF2B4 p.Ala228Thr Uncertain significance ★★ ⚠ same type
EIF2B4 p.Ala349Thr 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/eif2b4-p-glu10 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown