Is EIF4G1 p.Arg993= (c.2979C>T) pathogenic?

EIF4G1 p.Arg993= (c.2979C>T) is classified Likely benign in EIF4G1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-09-13). Rare (popmax 0.799%, afr); Associated with Parkinson disease 18, autosomal dominant, susceptibility to.

What condition is associated with EIF4G1 p.Arg993= (c.2979C>T)?

EIF4G1 p.Arg993= (c.2979C>T) is associated with Parkinson disease 18, autosomal dominant, susceptibility to (ClinVar).

How common is EIF4G1 p.Arg993= (c.2979C>T) in the general population?

EIF4G1 p.Arg993= (c.2979C>T) is rare (popmax 0.799%, afr) (gnomAD).

EIF4G1 p.Arg993=

c.2979C>T · rs11918961 · VCV1210075

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.799%, afr)

Conditions

Parkinson disease 18, autosomal dominant, susceptibility to

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.027	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.001	GERP 0.45, phastCons 0.78
Overall
CADD	5.661	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.799% African / African-American · 599/75,012 alleles

Filtering AF 0.746% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.725%

Overall 0.0427% 689/1,614,138 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.799%	125
Admixed American	0.07%	1,429
Remaining individualsnot grpmax-eligible	0.0624%	1,603
Middle Eastern	0.0495%	2,021
South Asian	0.0011%	91,084
European (non-Finnish)	0.000424%	236,009

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.Arg993=
Coding: c.2979C>T
MANE Select: NM_198241
dbSNP: rs11918961
Type: single nucleotide variant
Location: chr3:184325497 (GRCh38)
Gene constraint: LOEUF 0.048 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.06 · 14 PDB
Residue 993: the 'eif3/eif4a-binding' region

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

Disease context

Parkinson disease 18, autosomal dominant, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EIF4G1 p.Glu339Gln Uncertain significance ★★ ⚠ same condition
EIF4G1 p.Leu1275His Uncertain significance ★★ ⚠ same condition
EIF4G1 p.Pro1131His Uncertain significance ★★ ⚠ same condition
EIF4G1 p.Thr179Met Uncertain significance ★★ ⚠ same condition
EIF4G1 c.3325+16C>T Benign ★★ same condition
EIF4G1 c.3953+9A>G Benign ★★ same condition
EIF4G1 p.Leu1504= Benign/Likely benign ★★ same condition
EIF4G1 p.Met432Val Benign ★★ 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/eif4g1-p-arg993 (accessed [today's date]).

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