Is EIF4E1B p.Phe240Ser (c.719T>C) pathogenic?

EIF4E1B p.Phe240Ser (c.719T>C) is classified Uncertain significance in EIF4E1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-15). AlphaMissense: likely pathogenic (0.9157); Absent from gnomAD v4.1.

How common is EIF4E1B p.Phe240Ser (c.719T>C) in the general population?

EIF4E1B p.Phe240Ser (c.719T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF4E1B p.Phe240Ser (c.719T>C)?

AlphaMissense predicts likely pathogenic (score 0.9157) — an in-silico prediction, not a clinical call.

EIF4E1B p.Phe240Ser

c.719T>C · rs1219914553 · VCV2618678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9157 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9157	likely pathogenic
REVEL	0.49	indeterminate
SaProt	LLR -14.89	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,189 bp · p 0.22 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: EIF4E1B
Protein: p.Phe240Ser
Coding: c.719T>C
MANE Select: NM_001099408
dbSNP: rs1219914553
Type: single nucleotide variant
Location: chr5:176645970 (GRCh38)
Gene constraint: LOEUF 1.085 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.43

Full EIF4E1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF4E1B p.Ala195Val Uncertain significance ★ ⚠ same type
EIF4E1B p.Ala226Val Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg134Trp Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg147Ser Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg153Trp Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg172Gly Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg193Gly Uncertain significance ★ ⚠ same type
EIF4E1B p.Arg193Ser 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/eif4e1b-p-phe240ser (accessed [today's date]).

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