Is EIF4G1 p.Pro11= (c.33A>C) pathogenic?

EIF4G1 p.Pro11= (c.33A>C) is classified Likely benign in EIF4G1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). Common (popmax 15.3%, nfe) — too common for a highly-penetrant pathogenic allele.

EIF4G1 p.Pro11=

Q: How common is EIF4G1 p.Pro11= (c.33A>C) in the general population?

EIF4G1 p.Pro11= (c.33A>C) is common (popmax 15.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.33A>C · VCV4684743

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 15.3%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -2.9, phastCons 1
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.3% European (non-Finnish) · 60,370/393,690 alleles

Filtering AF 15.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.2%

Overall 10.1% 66,046/653,266 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	15.3%	7
Remaining individualsnot grpmax-eligible	9.52%	11
Middle Eastern	3.69%	27
Ashkenazi Jewishnot grpmax-eligible	2.52%	40
African / African-American	2.19%	46
South Asian	2.03%	49
East Asian	1.64%	61
Admixed American	0.214%	467
Finnishnot grpmax-eligible	0.151%	664

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: EIF4G1
Protein: p.Pro11=
Coding: c.33A>C
MANE Select: NM_198241
Type: single nucleotide variant
Location: chr3:184315829 (GRCh38)
Gene constraint: LOEUF 0.048 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.06 · 14 PDB
Residue 11: the 'disordered' region

Full EIF4G1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF4G1 p.Arg1163Trp Uncertain significance ★★ ⚠ same type
EIF4G1 p.Arg1590His Uncertain significance ★★ ⚠ same type
EIF4G1 p.Glu339Gln Uncertain significance ★★ ⚠ same type
EIF4G1 p.Glu870Ala Uncertain significance ★★ ⚠ same type
EIF4G1 p.Leu1275His Uncertain significance ★★ ⚠ same type
EIF4G1 p.Pro1131His Uncertain significance ★★ ⚠ same type
EIF4G1 p.Pro334Gln Uncertain significance ★★ ⚠ same type
EIF4G1 p.Ser558Phe 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/eif4g1-p-pro11 (accessed [today's date]).

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