Is EIF3F p.Pro19Ser (c.55C>T) pathogenic?

EIF3F p.Pro19Ser (c.55C>T) is classified Likely benign in EIF3F (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.0824); Rare (popmax 0.411%, afr); Associated with EIF3F-related disorder.

What condition is associated with EIF3F p.Pro19Ser (c.55C>T)?

EIF3F p.Pro19Ser (c.55C>T) is associated with EIF3F-related disorder (ClinVar).

How common is EIF3F p.Pro19Ser (c.55C>T) in the general population?

EIF3F p.Pro19Ser (c.55C>T) is rare (popmax 0.411%, afr) (gnomAD).

What do computational predictors say about EIF3F p.Pro19Ser (c.55C>T)?

AlphaMissense predicts likely benign (score 0.0824) — an in-silico prediction, not a clinical call.

EIF3F p.Pro19Ser

c.55C>T · rs139608264 · VCV3035552

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0824 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.411%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

EIF3F-related disorder

Computational evidence

Protein change
AlphaMissense	0.0824	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -8.49	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 -0.035	GERP -1.8
Regional constraint	o/e 1.40	unconstrained · MANE · 259 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	7.349	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 0.411% African / African-American · 308/74,988 alleles

Filtering AF 0.373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.358%

Overall 0.0211% 338/1,600,868 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.411%	243
Remaining individualsnot grpmax-eligible	0.0257%	3,898
Admixed American	0.02%	4,999
European (non-Finnish)	0.00017%	589,723

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.Pro19Ser
Coding: c.55C>T
MANE Select: NM_003754
dbSNP: rs139608264
Type: single nucleotide variant
Location: chr11:7987407 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.97 · 29 PDB
Residue 19: the 'disordered' region

Full EIF3F gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EIF3F-related disorder

Similar variants

EIF3F c.435+7G>A Likely benign same condition
EIF3F p.Ala76Gly Benign same condition
EIF3F p.Pro12Leu Benign same condition
EIF3F p.Pro39Leu Benign ⚠ same condition
EIF3F p.Pro4Ser Likely benign same condition
EIF3F p.Phe232Val Pathogenic/Likely pathogenic ★★ same type
EIF3F p.Arg306Cys Uncertain significance ★★ ⚠ same type
EIF3F p.Asn260Ser 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-pro19ser (accessed [today's date]).

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