Is EIF2B4 p.Ser290fs (c.868del) pathogenic?

EIF2B4 p.Ser290fs (c.868del) is classified Pathogenic in EIF2B4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). Very rare (popmax 0.00133%, afr).

How common is EIF2B4 p.Ser290fs (c.868del) in the general population?

EIF2B4 p.Ser290fs (c.868del) is very rare (popmax 0.00133%, afr) (gnomAD).

EIF2B4 p.Ser290fs

c.868del · rs767850637 · VCV2984742

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 0.92, phastCons 1
Overall
CADD	28.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,012 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,614,076 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,012
European (non-Finnish)	0.000593%	168,576

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.Ser290fs
Coding: c.868del
MANE Select: NM_001034116
dbSNP: rs767850637
Type: Deletion
Location: chr2:27367474 (GRCh38)
Gene constraint: LOEUF 0.687 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.37 · 38 PDB
Residue 290: a β-strand

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

Similar variants

EIF2B4 p.Gly55_Glu59del Uncertain significance ★★ same type
EIF2B4 p.Thr133_Glu136delinsLys Uncertain significance ★★ same type
EIF2B4 c.212-12del Benign/Likely benign ★★ same type
EIF2B4 c.1013+67_1169del Pathogenic ★ same type
EIF2B4 c.498+2_498+5del Likely pathogenic ★ same type
EIF2B4 c.66_75+18del Likely pathogenic ★ same type
EIF2B4 p.Cys444fs Pathogenic ★ same type
EIF2B4 p.Glu109fs 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/eif2b4-p-ser290fs (accessed [today's date]).

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