Is EIF3F p.Thr14= (c.42G>A) pathogenic?

EIF3F p.Thr14= (c.42G>A) is classified Likely benign in EIF3F (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.039%, nfe).

How common is EIF3F p.Thr14= (c.42G>A) in the general population?

EIF3F p.Thr14= (c.42G>A) is ultra-rare (popmax 0.039%, nfe) (gnomAD).

EIF3F p.Thr14=

c.42G>A · VCV4681380

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.039%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -2.4
Overall
CADD	2.161	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.039% European (non-Finnish) · 460/1,179,182 alleles

Filtering AF 0.036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0349%

Overall 0.0317% 507/1,599,422 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0433%	2,308
European (non-Finnish)grpmax	0.039%	2,563
Admixed American	0.0184%	5,447
South Asian	0.0055%	18,178
African / African-American	0.00535%	18,702

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr14=
Coding: c.42G>A
MANE Select: NM_003754
Type: single nucleotide variant
Location: chr11:7987394 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.97 · 29 PDB
Residue 14: the 'disordered' region

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

Similar variants

EIF3F p.Thr14Met 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.Thr303Ile Uncertain significance ★★ ⚠ same type
EIF3F c.*24C>T Benign ★★ 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-thr14 (accessed [today's date]).

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