Is EIF4B p.Arg401Pro (c.1202G>C) pathogenic?

EIF4B p.Arg401Pro (c.1202G>C) is classified Uncertain significance in EIF4B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely pathogenic (0.9148); Very rare (popmax 8.49e-05%, nfe).

How common is EIF4B p.Arg401Pro (c.1202G>C) in the general population?

EIF4B p.Arg401Pro (c.1202G>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about EIF4B p.Arg401Pro (c.1202G>C)?

AlphaMissense predicts likely pathogenic (score 0.9148) — an in-silico prediction, not a clinical call.

EIF4B p.Arg401Pro

c.1202G>C · VCV4663651

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9148 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9148	likely pathogenic
REVEL	0.521	indeterminate
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 0.96, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 5,675 bp · p 5.7e-08 · regional, not allelic
Overall
CADD	29.0	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

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,622 alleles

Overall 6.21e-05% 1/1,609,442 alleles · very rare exomes 1/1,457,072 · genomes 0/152,370 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EIF4B
Protein: p.Arg401Pro
Coding: c.1202G>C
MANE Select: NM_001417
Type: single nucleotide variant
Location: chr12:53034028 (GRCh38)
Gene constraint: LOEUF 0.176 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.91 · 3 PDB
Residue 401: the 'disordered' region

Full EIF4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF4B p.Arg401Gln Uncertain significance ★ ⚠ same residue
EIF4B p.Arg401Trp Uncertain significance ★ ⚠ same residue
EIF4B p.Ala204Gly Uncertain significance ★ ⚠ same type
EIF4B p.Ala364Val Uncertain significance ★ ⚠ same type
EIF4B p.Ala493Thr Uncertain significance ★ ⚠ same type
EIF4B p.Ala5Val Uncertain significance ★ ⚠ same type
EIF4B p.Ala65Ser Uncertain significance ★ ⚠ same type
EIF4B p.Arg202Cys 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/eif4b-p-arg401pro (accessed [today's date]).

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