Is ENG p.Glu485= (c.1455G>A) pathogenic?

ENG p.Glu485= (c.1455G>A) is classified Benign/Likely benign in ENG (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-21). Rare (popmax 0.169%, afr); Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Glu485= (c.1455G>A)?

ENG p.Glu485= (c.1455G>A) is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Glu485= (c.1455G>A) in the general population?

ENG p.Glu485= (c.1455G>A) is rare (popmax 0.169%, afr) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG p.Glu485=

c.1455G>A · rs150456852 · VCV385734

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.169%, 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 looked up on this page · why
Pangolin	Δ0.43	gain · loss 0.08 · independent
Constraint at this position
Conservation	phyloP 0.18	GERP -2.5, phastCons 0.005
Overall
CADD	15.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.169% African / African-American · 127/75,060 alleles

Filtering AF 0.145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.01% 162/1,613,934 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.169%	591
Remaining individualsnot grpmax-eligible	0.0368%	2,718
Middle Eastern	0.0165%	6,062
Admixed American	0.0133%	7,504
European (non-Finnish)	0.000254%	393,345

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.Glu485=
Coding: c.1455G>A
dbSNP: rs150456852
Type: single nucleotide variant
Location: chr9:127818351 (GRCh38)

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)

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-glu485 (accessed [today's date]).

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