What condition is associated with EIF3F p.Pro224Leu (c.671C>T)?

EIF3F p.Pro224Leu (c.671C>T) is associated with intellectual developmental disorder, autosomal recessive 67 (ClinVar).

How common is EIF3F p.Pro224Leu (c.671C>T) in the general population?

EIF3F p.Pro224Leu (c.671C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EIF3F p.Pro224Leu (c.671C>T)?

AlphaMissense predicts likely pathogenic (score 0.9873) — an in-silico prediction, not a clinical call.

EIF3F p.Pro224Leu

Q: Is EIF3F p.Pro224Leu (c.671C>T) pathogenic?

EIF3F p.Pro224Leu (c.671C>T) is classified Likely pathogenic in EIF3F (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9873); Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal recessive 67.

c.671C>T · rs1185010700 · VCV988781

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9873 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual developmental disorder, autosomal recessive 67

Computational evidence

Protein change
AlphaMissense	0.9873	likely pathogenic ✓ concordant with ClinVar
REVEL	0.396	indeterminate
SaProt	LLR -11.42	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 8,406 bp · p 4.6e-06 · regional, not allelic
Overall
CADD	29.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EIF3F
Protein: p.Pro224Leu
Coding: c.671C>T
MANE Select: NM_003754
dbSNP: rs1185010700
Type: single nucleotide variant
Location: chr11:7994443 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.97 · 29 PDB
Residue 224: a β-strand

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

Disease context

intellectual developmental disorder, autosomal recessive 67 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EIF3F p.Phe232Val Pathogenic/Likely pathogenic ★★ same condition
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

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-pro224leu (accessed [today's date]).

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