Is ENG p.Leu8fs (c.22_23del) pathogenic?

ENG p.Leu8fs (c.2223del) is classified Pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Leu8fs (c.22_23del)?

ENG p.Leu8fs (c.22_23del) is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How is Hereditary hemorrhagic telangiectasia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ENG p.Leu8fs

c.22_23del · VCV3682777

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary hemorrhagic telangiectasia

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 1 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.4	GERP -0.71

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

Variant & gene context

Gene: ENG
Protein: p.Leu8fs
Coding: c.22_23del
MANE Select: NM_001114753
Type: Microsatellite
Location: chr9:127854333 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 8: a UniProt-annotated variant site (in hht1)

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

Disease context

hereditary hemorrhagic telangiectasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary hemorrhagic telangiectasia (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ENG p.Leu8Pro Pathogenic/Likely pathogenic ★★ ⚠ same residue
ENG p.Arg153fs Pathogenic/Likely pathogenic ★★ same condition
ENG p.Arg478fs Pathogenic ★★ same condition
ENG p.Gly214fs Pathogenic ★★ same condition
ENG p.Pro296fs Pathogenic/Likely pathogenic ★★ same condition
ENG p.Ser449fs Pathogenic ★★ same condition
ENG p.Thr200fs Pathogenic ★★ same condition
ENG p.Thr45fs 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/eng-p-leu8fs (accessed [today's date]).

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