Is EIF4A3 p.Pro312Ser (c.934C>T) pathogenic?

EIF4A3 p.Pro312Ser (c.934C>T) is classified Uncertain significance in EIF4A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.2853); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EIF4A3 p.Pro312Ser (c.934C>T)?

EIF4A3 p.Pro312Ser (c.934C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EIF4A3 p.Pro312Ser (c.934C>T) in the general population?

EIF4A3 p.Pro312Ser (c.934C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF4A3 p.Pro312Ser (c.934C>T)?

AlphaMissense predicts likely benign (score 0.2853) — an in-silico prediction, not a clinical call.

EIF4A3 p.Pro312Ser

c.934C>T · VCV4618372

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2853 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2853	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -3.6, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 3,655 bp · p 1e-28 · regional, not allelic
Overall
CADD	24.7	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

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: EIF4A3
Protein: p.Pro312Ser
Coding: c.934C>T
MANE Select: NM_014740
Type: single nucleotide variant
Location: chr17:80137435 (GRCh38)
Gene constraint: LOEUF 0.084 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.93 · 24 PDB
Residue 312: the helicase c-terminal domain

Full EIF4A3 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

EIF4A3 c.587-5C>G Conflicting classifications of pathogenicity ★ same condition
EIF4A3 p.Ala13Val Uncertain significance ★ ⚠ same condition
EIF4A3 p.Arg16Pro Uncertain significance ★ ⚠ same condition
EIF4A3 p.Arg172Cys Uncertain significance ★ ⚠ same condition
EIF4A3 p.Arg238His Uncertain significance ★ ⚠ same condition
EIF4A3 p.Arg238Leu Uncertain significance ★ ⚠ same condition
EIF4A3 p.Arg51Trp Uncertain significance ★ ⚠ same condition
EIF4A3 p.Asn145Ser 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/eif4a3-p-pro312ser (accessed [today's date]).

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