Is EIF4A2 p.Lys248= (c.744A>G) pathogenic?

EIF4A2 p.Lys248= (c.744A>G) is classified Benign in EIF4A2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-27). Common (popmax 8.12%, eas) — too common for a highly-penetrant pathogenic allele; Associated with EIF4A2-related disorder.

What condition is associated with EIF4A2 p.Lys248= (c.744A>G)?

EIF4A2 p.Lys248= (c.744A>G) is associated with EIF4A2-related disorder (ClinVar).

EIF4A2 p.Lys248=

Q: How common is EIF4A2 p.Lys248= (c.744A>G) in the general population?

EIF4A2 p.Lys248= (c.744A>G) is common (popmax 8.12%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.744A>G · rs11538612 · VCV3042243

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 8.12%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

EIF4A2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.56, phastCons 1
Overall
CADD	7.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.12% East Asian · 3,646/44,874 alleles

Filtering AF 7.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.82%

Overall 1.01% 16,358/1,614,050 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	8.12%	12
South Asian	4.39%	23
Middle Eastern	2%	50
Remaining individualsnot grpmax-eligible	1.27%	79
African / African-American	1.16%	86
European (non-Finnish)	0.55%	182
Admixed American	0.483%	207
Ashkenazi Jewishnot grpmax-eligible	0.263%	380
Finnishnot grpmax-eligible	0.108%	928

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.Lys248=
Coding: c.744A>G
MANE Select: NM_001967
dbSNP: rs11538612
Type: single nucleotide variant
Location: chr3:186786618 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 1 PDB
Residue 248: the helicase c-terminal domain

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

Disease context

EIF4A2-related disorder

Similar variants

EIF4A2 p.Arg335His Uncertain significance ★ ⚠ same condition
EIF4A2 p.Lys248fs Uncertain significance ★ same residue
EIF4A2 c.518-7C>T Benign same condition
EIF4A2 c.771+5C>T Likely benign same condition
EIF4A2 c.772-3C>T Benign same condition
EIF4A2 c.-8T>C Likely benign same condition
EIF4A2 p.Phe376= Likely benign same condition
EIF4A2 p.Tyr8= Likely benign 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/eif4a2-p-lys248 (accessed [today's date]).

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