Is ENG c.*273A>C pathogenic?

ENG c.273A>C is classified Uncertain significance in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Ultra-rare (popmax 0.019%, nfe); Associated with telangiectasia, hereditary hemorrhagic, type 1.

What condition is associated with ENG c.*273A>C?

ENG c.*273A>C is associated with telangiectasia, hereditary hemorrhagic, type 1 (ClinVar).

How common is ENG c.*273A>C in the general population?

ENG c.*273A>C is ultra-rare (popmax 0.019%, nfe) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG c.*273A>C

rs138178682 · VCV365079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.019%, nfe)

Conditions

telangiectasia, hereditary hemorrhagic, type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -3.6
Overall
CADD	5.319	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.019% European (non-Finnish) · 58/305,608 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0111% 58/524,662 alleles · ultra-rare

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.*273A>C
MANE Select: NM_001114753
dbSNP: rs138178682
Type: single nucleotide variant
Location: chr9:127815409 (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

telangiectasia, hereditary hemorrhagic, type 1 — 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.Arg529His Pathogenic ★★★ ⚠ same condition
ENG p.Asn423Ser Likely pathogenic ★★★ ⚠ same condition
ENG p.Cys382Tyr Pathogenic ★★★ same condition
ENG p.Cys549Gly Likely pathogenic ★★★ same condition
ENG p.Gly331Ser Pathogenic ★★★ ⚠ same condition
ENG p.Gly603Arg Likely pathogenic ★★★ same condition
ENG p.Leu221Pro Likely pathogenic ★★★ same condition
ENG p.Leu506His Likely 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-star-273a-c (accessed [today's date]).

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