Is ENG c.-70del pathogenic?

ENG c.-70del is classified Uncertain significance in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). Ultra-rare (popmax 0.0432%, eas); Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG c.-70del?

ENG c.-70del is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG c.-70del in the general population?

ENG c.-70del is ultra-rare (popmax 0.0432%, eas) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG c.-70del

rs886063477 · VCV365099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0432%, eas)

Conditions

hereditary hemorrhagic telangiectasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.21	GERP -1.5, phastCons 0.066
Non-coding constraint	Z 3.30	1 kb window · o/e 0.70 · regional · uncalibrated
Overall
CADD	13.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0432% East Asian · 17/39,386 alleles

Filtering AF 0.0275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0226%

Overall 0.00126% 19/1,506,382 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0432%	2,317
African / African-American	0.00141%	71,154
European (non-Finnish)	8.96e-05%	1,116,331

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ENG
Coding: c.-70del
MANE Select: NM_001114753
dbSNP: rs886063477
Type: Deletion
Location: chr9:127854425 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB

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.1687delG Pathogenic ★★ same condition
ENG p.Ala55fs Pathogenic ★★ same condition
ENG p.Arg232_Thr233del Likely pathogenic ★★ same condition
ENG p.Arg399fs Pathogenic/Likely pathogenic ★★ same condition
ENG p.Asn163fs Pathogenic/Likely pathogenic ★★ same condition
ENG p.Asn423fs Pathogenic ★★ same condition
ENG p.Asp578fs Pathogenic/Likely pathogenic ★★ same condition
ENG p.Cys493fs 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-c-minus-70del (accessed [today's date]).

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