Is EIF4E2 p.Val102Ile (c.304G>A) pathogenic?

EIF4E2 p.Val102Ile (c.304G>A) is classified Uncertain significance in EIF4E2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.1076); No allele count reported in gnomAD v4.1 (AN 1,599,252).

How common is EIF4E2 p.Val102Ile (c.304G>A) in the general population?

EIF4E2 p.Val102Ile (c.304G>A) is no allele count reported in gnomAD v4.1 (AN 1,599,252) (gnomAD).

What do computational predictors say about EIF4E2 p.Val102Ile (c.304G>A)?

AlphaMissense predicts likely benign (score 0.1076) — an in-silico prediction, not a clinical call.

EIF4E2 p.Val102Ile

c.304G>A · rs2469440979 · VCV2244645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1076 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,599,252)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1076	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -9.19	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 11 kb · p 1.1e-10 · regional, not allelic
Overall
CADD	22.8	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

No allele count reported in gnomAD v4.1 (AN 1,599,252). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EIF4E2
Protein: p.Val102Ile
Coding: c.304G>A
MANE Select: NM_004846
dbSNP: rs2469440979
Type: single nucleotide variant
Location: chr2:232564280 (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-val102ile (accessed [today's date]).

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