Is EIF4A2 p.Ser343Pro (c.1027T>C) pathogenic?

EIF4A2 p.Ser343Pro (c.1027T>C) is classified Uncertain significance in EIF4A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: likely pathogenic (0.9942); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EIF4A2 p.Ser343Pro (c.1027T>C)?

EIF4A2 p.Ser343Pro (c.1027T>C) is associated with Inborn genetic diseases (ClinVar).

How common is EIF4A2 p.Ser343Pro (c.1027T>C) in the general population?

EIF4A2 p.Ser343Pro (c.1027T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF4A2 p.Ser343Pro (c.1027T>C)?

AlphaMissense predicts likely pathogenic (score 0.9942) — an in-silico prediction, not a clinical call.

EIF4A2 p.Ser343Pro

c.1027T>C · VCV3844152

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9942 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9942	likely pathogenic
REVEL	0.468	indeterminate
SaProt	LLR -14.90	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 42 bp · p 0.022 · regional, not allelic
Overall
CADD	27.0	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: EIF4A2
Protein: p.Ser343Pro
Coding: c.1027T>C
MANE Select: NM_001967
Type: single nucleotide variant
Location: chr3:186787830 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.94 · 1 PDB
Residue 343: the helicase c-terminal domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EIF4A2 p.Ser343Phe Uncertain significance ★ ⚠ same residue
EIF4A2 p.Gly362Ser Pathogenic ★★ same condition
EIF4A2 p.Ile278Thr Uncertain significance ★★ ⚠ same condition
EIF4A2 p.Asp338Tyr Likely pathogenic ★ same condition
EIF4A2 p.Ala302Ser Uncertain significance ★ ⚠ same condition
EIF4A2 p.Ala6Thr Uncertain significance ★ ⚠ same condition
EIF4A2 p.Asn27Ser Uncertain significance ★ ⚠ same condition
EIF4A2 p.Gln249Glu Uncertain significance ★ ⚠ 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-ser343pro (accessed [today's date]).

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