Is EIF3F p.Pro17Ala (c.49C>G) pathogenic?

EIF3F p.Pro17Ala (c.49C>G) is classified Uncertain significance in EIF3F (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-01). AlphaMissense: likely benign (0.0465); Very rare (popmax 0.00178%, nfe).

How common is EIF3F p.Pro17Ala (c.49C>G) in the general population?

EIF3F p.Pro17Ala (c.49C>G) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about EIF3F p.Pro17Ala (c.49C>G)?

AlphaMissense predicts likely benign (score 0.0465) — an in-silico prediction, not a clinical call.

EIF3F p.Pro17Ala

c.49C>G · rs750034387 · VCV3025223

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0465 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0465	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -8.07	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.69	GERP -2.5
Regional constraint	o/e 1.40	unconstrained · MANE · 259 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	9.752	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00178% European (non-Finnish) · 21/1,179,482 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00137% 22/1,600,510 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,166
Remaining individualsnot grpmax-eligible	0.0016%	62,348

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.Pro17Ala
Coding: c.49C>G
MANE Select: NM_003754
dbSNP: rs750034387
Type: single nucleotide variant
Location: chr11:7987401 (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

Similar variants

EIF3F p.Pro17Arg Uncertain significance ★ ⚠ same residue
EIF3F p.Pro17Gln Uncertain significance ★ ⚠ same residue
EIF3F p.Phe232Val Pathogenic/Likely pathogenic ★★ same type
EIF3F p.Arg306Cys Uncertain significance ★★ ⚠ same type
EIF3F p.Asn260Ser Uncertain significance ★★ same type
EIF3F p.Asp292Glu Uncertain significance ★★ ⚠ same type
EIF3F p.Ser267Gly Uncertain significance ★★ ⚠ same type
EIF3F p.Thr14Met 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/eif3f-p-pro17ala (accessed [today's date]).

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