Is EIF3F p.Pro17Arg (c.50C>G) pathogenic?

EIF3F p.Pro17Arg (c.50C>G) is classified Uncertain significance in EIF3F (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). AlphaMissense: likely benign (0.1569); Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with EIF3F p.Pro17Arg (c.50C>G)?

EIF3F p.Pro17Arg (c.50C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EIF3F p.Pro17Arg (c.50C>G) in the general population?

EIF3F p.Pro17Arg (c.50C>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about EIF3F p.Pro17Arg (c.50C>G)?

AlphaMissense predicts likely benign (score 0.1569) — an in-silico prediction, not a clinical call.

EIF3F p.Pro17Arg

c.50C>G · VCV3507582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1569 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1569	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -12.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.2, phastCons 0.07
Regional constraint	o/e 1.40	unconstrained · MANE · 259 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	16.38	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 0.00334% Admixed American · 2/59,962 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000125% 2/1,600,598 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: EIF3F
Protein: p.Pro17Arg
Coding: c.50C>G
MANE Select: NM_003754
Type: single nucleotide variant
Location: chr11:7987402 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.97 · 29 PDB
Residue 17: the 'disordered' region

Full EIF3F 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

EIF3F p.Pro17Ala Uncertain significance ★ ⚠ same residue
EIF3F p.Pro17Gln Uncertain significance ★ ⚠ same residue
EIF3F p.Asp292Glu Uncertain significance ★★ ⚠ same condition
EIF3F p.Pro7Ser Likely benign ★★ ⚠ same condition
EIF3F c.365-3C>T Uncertain significance ★ same condition
EIF3F p.Ala300Thr Uncertain significance ★ ⚠ same condition
EIF3F p.Ala44Val Uncertain significance ★ ⚠ same condition
EIF3F p.Ala51Gly 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/eif3f-p-pro17arg (accessed [today's date]).

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