Is EIF3F p.Pro7= (c.21A>G) pathogenic?

EIF3F p.Pro7= (c.21A>G) is classified Likely benign in EIF3F (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-01). Rare (popmax 0.13%, nfe).

How common is EIF3F p.Pro7= (c.21A>G) in the general population?

EIF3F p.Pro7= (c.21A>G) is rare (popmax 0.13%, nfe) (gnomAD).

EIF3F p.Pro7=

c.21A>G · rs148453570 · VCV2498504

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.13%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	donor gain · deltas
Pangolin	Δ0.26	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.4	GERP -2.6
Overall
CADD	3.037	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.13% European (non-Finnish) · 1,537/1,178,022 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.123%

Overall 0.119% 1,908/1,596,814 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.607%	165
Remaining individualsnot grpmax-eligible	0.14%	716
European (non-Finnish)grpmax	0.13%	766
Admixed American	0.114%	878
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0374%	2,673
Finnishnot grpmax-eligible	0.00599%	16,699
East Asian	0.00447%	22,357
South Asian	0.0033%	30,259

Ashkenazi Jewish 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.Pro7=
Coding: c.21A>G
MANE Select: NM_003754
dbSNP: rs148453570
Type: single nucleotide variant
Location: chr11:7987373 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.97 · 29 PDB
Residue 7: the 'disordered' region

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

Similar variants

EIF3F p.Pro7Ser Likely benign ★★ ⚠ 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
EIF3F p.Thr303Ile 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-pro7 (accessed [today's date]).

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