Is EIF3F p.Pro49Ser (c.145C>T) pathogenic?

EIF3F p.Pro49Ser (c.145C>T) is classified Uncertain significance in EIF3F (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.0681); Ultra-rare (popmax 0.0205%, mid); Associated with Inborn genetic diseases.

What condition is associated with EIF3F p.Pro49Ser (c.145C>T)?

EIF3F p.Pro49Ser (c.145C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EIF3F p.Pro49Ser (c.145C>T) in the general population?

EIF3F p.Pro49Ser (c.145C>T) is ultra-rare (popmax 0.0205%, mid) (gnomAD).

What do computational predictors say about EIF3F p.Pro49Ser (c.145C>T)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

EIF3F p.Pro49Ser

c.145C>T · VCV4618366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0205%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.40	unconstrained · MANE · 259 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	9.65	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 0.0205% Middle Eastern · 1/4,888 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000972%

Overall 0.00162% 26/1,606,368 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0205%	4,888
Remaining individualsnot grpmax-eligible	0.00322%	31,039
South Asian	0.00221%	45,319
European (non-Finnish)	0.00178%	56,093

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.Pro49Ser
Coding: c.145C>T
MANE Select: NM_003754
Type: single nucleotide variant
Location: chr11:7987497 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.97 · 29 PDB
Residue 49: 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.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
EIF3F p.Ala81Gly Uncertain significance ★ ⚠ same condition
EIF3F p.Arg192Gln 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-pro49ser (accessed [today's date]).

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