Is ENG c.1272+20del pathogenic?

ENG c.1272+20del is classified Benign in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-25). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG c.1272+20del?

ENG c.1272+20del is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG c.1272+20del in the general population?

ENG c.1272+20del is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG c.1272+20del

rs1469810672 · VCV2751045

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hereditary hemorrhagic telangiectasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +20	near-intronic (+20 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.82	GERP -2.4
Non-coding constraint	Z 1.43	1 kb window · o/e 0.89 · regional · uncalibrated
Overall
CADD	0.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,054 alleles

Overall 0.000124% 2/1,614,094 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	64,008
European (non-Finnish)grpmax	8.47e-05%	1,180,054

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.1272+20del
MANE Select: NM_001114753
dbSNP: rs1469810672
Type: Deletion
Location: chr9:127819880 (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-1272-plus-20del (accessed [today's date]).

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