Is EFTUD2 p.Ile552fs (c.1655_1656insG) pathogenic?

EFTUD2 p.Ile552fs (c.16551656insG) is classified Pathogenic in EFTUD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). Associated with mandibulofacial dysostosis-microcephaly syndrome.

What condition is associated with EFTUD2 p.Ile552fs (c.1655_1656insG)?

EFTUD2 p.Ile552fs (c.1655_1656insG) is associated with mandibulofacial dysostosis-microcephaly syndrome (ClinVar).

EFTUD2 p.Ile552fs

c.1655_1656insG · VCV4850695

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

mandibulofacial dysostosis-microcephaly syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 17 of 28
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: EFTUD2
Protein: p.Ile552fs
Coding: c.1655_1656insG
MANE Select: NM_004247
Type: Insertion
Location: chr17:44860495 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 89.94 · 72 PDB
Residue 552: a β-strand

Full EFTUD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mandibulofacial dysostosis-microcephaly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EFTUD2 p.Ile552Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
EFTUD2 c.1058+1G>A Pathogenic ★★ same condition
EFTUD2 c.1414-2A>G Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 c.1607+1G>T Likely pathogenic ★★ same condition
EFTUD2 c.2133-2A>G Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 c.2562-2_2562-1del Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 c.2562-2A>G Pathogenic/Likely pathogenic ★★ same condition
EFTUD2 c.2562-2del Pathogenic ★★ 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/eftud2-p-ile552fs (accessed [today's date]).

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