Is EIF4A3 p.Arg16Pro (c.47G>C) pathogenic?

EIF4A3 p.Arg16Pro (c.47G>C) is classified Uncertain significance in EIF4A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: ambiguous (0.343); Very rare (popmax 0.0081%, afr); Associated with Inborn genetic diseases.

What condition is associated with EIF4A3 p.Arg16Pro (c.47G>C)?

EIF4A3 p.Arg16Pro (c.47G>C) is associated with Inborn genetic diseases (ClinVar).

How common is EIF4A3 p.Arg16Pro (c.47G>C) in the general population?

EIF4A3 p.Arg16Pro (c.47G>C) is very rare (popmax 0.0081%, afr) (gnomAD).

What do computational predictors say about EIF4A3 p.Arg16Pro (c.47G>C)?

AlphaMissense predicts ambiguous (score 0.343) — an in-silico prediction, not a clinical call.

EIF4A3 p.Arg16Pro

c.47G>C · VCV4247852

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.343 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0081%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.343	ambiguous
REVEL	0.142	moderately benign-leaning
SaProt	LLR -5.79	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 0.65, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 86 bp · p 0.53 · regional, not allelic
Overall
CADD	25.9	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 0.0081% African / African-American · 6/74,102 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000373% 6/1,609,578 alleles · very rare

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: EIF4A3
Protein: p.Arg16Pro
Coding: c.47G>C
MANE Select: NM_014740
Type: single nucleotide variant
Location: chr17:80146915 (GRCh38)
Gene constraint: LOEUF 0.084 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.93 · 24 PDB

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.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
EIF4A3 p.Gln66Lys 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-arg16pro (accessed [today's date]).

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