Is EIF3F p.Val217Ile (c.649G>A) pathogenic?

EIF3F p.Val217Ile (c.649G>A) is classified Uncertain significance in EIF3F (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely benign (0.089); Rare (popmax 0.142%, eas).

How common is EIF3F p.Val217Ile (c.649G>A) in the general population?

EIF3F p.Val217Ile (c.649G>A) is rare (popmax 0.142%, eas) (gnomAD).

What do computational predictors say about EIF3F p.Val217Ile (c.649G>A)?

AlphaMissense predicts likely benign (score 0.089) — an in-silico prediction, not a clinical call.

EIF3F p.Val217Ile

c.649G>A · rs189875301 · VCV1879199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.089 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.142%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.089	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.04	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 4.5	GERP 0.86, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,406 bp · p 4.6e-06 · regional, not allelic
Overall
CADD	20.6	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 0.142% East Asian · 63/44,350 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.0059% 94/1,593,494 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.142%	704
South Asian	0.0217%	4,618
Remaining individualsnot grpmax-eligible	0.00649%	15,399
African / African-American	0.00134%	74,606
European (non-Finnish)	0.000599%	167,054

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.Val217Ile
Coding: c.649G>A
MANE Select: NM_003754
dbSNP: rs189875301
Type: single nucleotide variant
Location: chr11:7993020 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.97 · 29 PDB
Residue 217: the mpn domain; a β-strand

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

Similar variants

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
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-val217ile (accessed [today's date]).

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