Is ENG p.Ile575del (c.1721TCA[1]) pathogenic?

ENG p.Ile575del (c.1721TCA[1]) is classified Uncertain significance in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-05). Ultra-rare (popmax 0.012%, afr); Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Ile575del (c.1721TCA[1])?

ENG p.Ile575del (c.1721TCA[1]) is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Ile575del (c.1721TCA[1]) in the general population?

ENG p.Ile575del (c.1721TCA[1]) is ultra-rare (popmax 0.012%, afr) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG p.Ile575del

c.1721TCA[1] · rs777038953 · VCV577833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

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 2.7	GERP -0.62, phastCons 1
Overall
CADD	13.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,936 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00062% 10/1,614,032 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,326
European (non-Finnish)	8.47e-05%	1,179,986

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
Protein: p.Ile575del
Coding: c.1721TCA[1]
MANE Select: NM_001114753
dbSNP: rs777038953
Type: Microsatellite
Location: chr9:127817164 (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 p.Ile575Met Uncertain significance ★★ ⚠ same residue
ENG p.Ile575Thr Uncertain significance ★ ⚠ 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

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-ile575del (accessed [today's date]).

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