Is EIF4E p.Ile63Val (c.187A>G) pathogenic?

EIF4E p.Ile63Val (c.187A>G) is classified Uncertain significance in EIF4E (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: ambiguous (0.3793); Absent from gnomAD v4.1.

How common is EIF4E p.Ile63Val (c.187A>G) in the general population?

EIF4E p.Ile63Val (c.187A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF4E p.Ile63Val (c.187A>G)?

AlphaMissense predicts ambiguous (score 0.3793) — an in-silico prediction, not a clinical call.

EIF4E p.Ile63Val

c.187A>G · rs2530444672 · VCV2325901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3793 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3793	ambiguous
REVEL	0.42	indeterminate
SaProt	LLR -4.69	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.72, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 21 kb · p 1.6e-23 · regional, not allelic
Overall
CADD	22.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EIF4E
Protein: p.Ile63Val
Coding: c.187A>G
MANE Select: NM_001968
dbSNP: rs2530444672
Type: single nucleotide variant
Location: chr4:98891271 (GRCh38)
Gene constraint: LOEUF 0.09 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.48 · 45 PDB
Residue 63: a β-strand

Full EIF4E gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF4E c.18+1G>T Uncertain significance ★ same type
EIF4E c.399+599C>T Uncertain significance ★ same type
EIF4E p.Ala29Thr Uncertain significance ★ ⚠ same type
EIF4E p.Arg109Leu Uncertain significance ★ ⚠ same type
EIF4E p.Arg181Met Uncertain significance ★ same type
EIF4E p.Asn41Ser Uncertain significance ★ ⚠ same type
EIF4E p.Glu5Lys Uncertain significance ★ ⚠ same type
EIF4E p.Gly196Ser 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/eif4e-p-ile63val (accessed [today's date]).

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