Is EIF4A2 p.Thr299fs (c.896_897del) pathogenic?

EIF4A2 p.Thr299fs (c.896897del) is classified Uncertain significance in EIF4A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-11). Very rare (popmax 0.000169%, nfe).

How common is EIF4A2 p.Thr299fs (c.896_897del) in the general population?

EIF4A2 p.Thr299fs (c.896_897del) is very rare (popmax 0.000169%, nfe) (gnomAD).

EIF4A2 p.Thr299fs

c.896_897del · rs1721782941 · VCV2504658

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 8 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,984 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,842 alleles · very rare

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: EIF4A2
Protein: p.Thr299fs
Coding: c.896_897del
MANE Select: NM_001967
dbSNP: rs1721782941
Type: Microsatellite
Location: chr3:186787249 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 1 PDB
Residue 299: the helicase c-terminal domain

Full EIF4A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF4A2 p.Leu44fs Likely pathogenic ★★ same type
EIF4A2 p.Ser79fs Likely pathogenic ★ same type
EIF4A2 p.Arg312fs Uncertain significance ★ same type
EIF4A2 p.Met166fs Uncertain significance ★ same type
EIF4A2 p.Ser207fs Uncertain significance ★ same type
EIF4A2 p.Arg62fs Pathogenic same type
EIF4A2 p.Asp37del Likely pathogenic same type
EIF4A2 p.Glu257fs 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/eif4a2-p-thr299fs (accessed [today's date]).

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