Is ENG p.Ala160fs (c.478dup) pathogenic?

ENG p.Ala160fs (c.478dup) is classified Pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). Absent from gnomAD; Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Ala160fs (c.478dup)?

ENG p.Ala160fs (c.478dup) is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Ala160fs (c.478dup) in the general population?

ENG p.Ala160fs (c.478dup) is absent from gnomAD (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG p.Ala160fs

c.478dup · rs2539077738 · VCV2703153

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 4 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ENG
Protein: p.Ala160fs
Coding: c.478dup
MANE Select: NM_001114753
dbSNP: rs2539077738
Type: Duplication
Location: chr9:127826554 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 160: a β-strand; a disulfide bond; a UniProt-annotated variant site (in hht1); the 'required for interaction with gdf2' region; the 'or2' 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 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
ENG p.Thr361fs 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-ala160fs (accessed [today's date]).

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