Is ENG p.Glu302fs (c.903_904dup) pathogenic?

ENG p.Glu302fs (c.903904dup) is classified Pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-11). Ultra-rare (gnomAD MAF 7.141e-07); Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Glu302fs (c.903_904dup)?

ENG p.Glu302fs (c.903_904dup) is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Glu302fs (c.903_904dup) in the general population?

ENG p.Glu302fs (c.903_904dup) is ultra-rare (gnomAD MAF 7.141e-07) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG p.Glu302fs

c.903_904dup · rs1554810177 · VCV3068695

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.141e-07)

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 7 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.8	GERP -0.89, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 7.14e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: ENG
Protein: p.Glu302fs
Coding: c.903_904dup
MANE Select: NM_001114753
dbSNP: rs1554810177
Type: Duplication
Location: chr9:127824886 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 302: an α-helix; a disulfide bond; the 'required for interaction with gdf2' region; the 'or1, c-terminal part' region

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.Glu302Ter Pathogenic ★★ same residue
ENG c.360+2dup Pathogenic/Likely pathogenic ★★ same condition
ENG p.Arg199fs Pathogenic ★★ same condition
ENG p.Gln166fs Pathogenic/Likely pathogenic ★★ same condition
ENG p.Gln188fs Pathogenic ★★ same condition
ENG p.Glu239fs Pathogenic ★★ same condition
ENG p.Lys543fs Pathogenic ★★ same condition
ENG p.Ser433fs 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-glu302fs (accessed [today's date]).

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