Is EIF4E2 p.Pro240Arg (c.719C>G) pathogenic?

EIF4E2 p.Pro240Arg (c.719C>G) is classified Uncertain significance in EIF4E2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.143); Very rare (popmax 0.004%, afr).

How common is EIF4E2 p.Pro240Arg (c.719C>G) in the general population?

EIF4E2 p.Pro240Arg (c.719C>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about EIF4E2 p.Pro240Arg (c.719C>G)?

AlphaMissense predicts likely benign (score 0.143) — an in-silico prediction, not a clinical call.

EIF4E2 p.Pro240Arg

c.719C>G · rs779845297 · VCV3088000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.143 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.143	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2.3, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 64 bp · p 0.47 · regional, not allelic
Overall
CADD	19.95	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,908 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00105% 17/1,614,054 alleles · very rare exomes 12/1,461,858 · genomes 5/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,969
European (non-Finnish)	0.00119%	84,289

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: EIF4E2
Protein: p.Pro240Arg
Coding: c.719C>G
MANE Select: NM_004846
dbSNP: rs779845297
Type: single nucleotide variant
Location: chr2:232568998 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 80.42 · 7 PDB

Full EIF4E2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF4E2 p.Ala7Thr Uncertain significance ★ ⚠ same type
EIF4E2 p.Arg103His Uncertain significance ★ ⚠ same type
EIF4E2 p.Arg146His Uncertain significance ★ ⚠ same type
EIF4E2 p.Arg174Cys Uncertain significance ★ ⚠ same type
EIF4E2 p.Arg197Gln Uncertain significance ★ ⚠ same type
EIF4E2 p.Arg197Trp Uncertain significance ★ ⚠ same type
EIF4E2 p.Arg231Gly Uncertain significance ★ ⚠ same type
EIF4E2 p.Arg241Gln 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/eif4e2-p-pro240arg (accessed [today's date]).

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