Is EIF3F p.Phe232Val (c.694T>G) pathogenic?

EIF3F p.Phe232Val (c.694T>G) is classified Pathogenic/Likely pathogenic in EIF3F (ClinVar, Multiple submitters, 36 submitters; last evaluated 2026-06-24). AlphaMissense: likely pathogenic (0.9997); Rare (popmax 0.157%, nfe); Associated with neurodevelopmental disorder.

What condition is associated with EIF3F p.Phe232Val (c.694T>G)?

EIF3F p.Phe232Val (c.694T>G) is associated with neurodevelopmental disorder, intellectual disability, intellectual developmental disorder, autosomal recessive 67 (ClinVar).

How common is EIF3F p.Phe232Val (c.694T>G) in the general population?

EIF3F p.Phe232Val (c.694T>G) is rare (popmax 0.157%, nfe) (gnomAD).

What do computational predictors say about EIF3F p.Phe232Val (c.694T>G)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

EIF3F p.Phe232Val

c.694T>G · rs141976414 · VCV617475

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 36 submitters

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.157%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 6% in EIF3F
REVEL	0.759	pathogenic-leaning
SaProt	LLR -12.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 0.76, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,406 bp · p 4.6e-06 · regional, not allelic
Overall
CADD	28.9	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 0.157% European (non-Finnish) · 1,854/1,179,998 alleles

Filtering AF 0.151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.149%

Overall 0.125% 2,020/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.182%	548
European (non-Finnish)grpmax	0.157%	636
Remaining individualsnot grpmax-eligible	0.107%	933
Admixed American	0.0367%	2,728
African / African-American	0.0227%	4,414
South Asian	0.00439%	22,762
Finnishnot grpmax-eligible	0.00312%	32,014

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.Phe232Val
Coding: c.694T>G
MANE Select: NM_003754
dbSNP: rs141976414
Type: single nucleotide variant
Location: chr11:7994466 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.97 · 29 PDB
Residue 232: a UniProt-annotated variant site (in mrt67; decreased protein abundance); a β-strand

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

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability intellectual developmental disorder, autosomal recessive 67 neurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Similar variants

EIF3F p.Arg306Cys Uncertain significance ★★ ⚠ same condition
EIF3F p.Thr14Met Uncertain significance ★★ ⚠ same condition
EIF3F p.Thr303Ile Uncertain significance ★★ ⚠ same condition
EIF3F c.*24C>T Benign ★★ same condition
EIF3F p.His187= Benign ★★ same condition
EIF3F c.653+3G>T Uncertain significance ★ same condition
EIF3F p.Asn342Ser Uncertain significance ★ ⚠ same condition
EIF3F p.Gly88Asp 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-phe232val (accessed [today's date]).

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