Is ENG p.Asp365= (c.1095C>T) pathogenic?

ENG p.Asp365= (c.1095C>T) is classified Likely benign in ENG (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-07). Ultra-rare (popmax 0.0667%, amr); Associated with telangiectasia, hereditary hemorrhagic, type 1.

What condition is associated with ENG p.Asp365= (c.1095C>T)?

ENG p.Asp365= (c.1095C>T) is associated with telangiectasia, hereditary hemorrhagic, type 1, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Asp365= (c.1095C>T) in the general population?

ENG p.Asp365= (c.1095C>T) is ultra-rare (popmax 0.0667%, amr) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG p.Asp365=

c.1095C>T · rs142803546 · VCV365089

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, amr)

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 -6.3	GERP -3.5
Overall
CADD	0.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0667% Admixed American · 40/59,996 alleles

Filtering AF 0.0548% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0534%

Overall 0.0486% 785/1,613,980 alleles · ultra-rare exomes 731/1,461,874 · genomes 54/152,106 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0667%	1,500
European (non-Finnish)	0.0585%	1,710
South Asian	0.0329%	3,035
Remaining individualsnot grpmax-eligible	0.0304%	3,289
African / African-American	0.00667%	14,994
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Asp365=
Coding: c.1095C>T
MANE Select: NM_001114753
dbSNP: rs142803546
Type: single nucleotide variant
Location: chr9:127824343 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 365: a β-strand; the zp domain

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

Also linked: hereditary hemorrhagic telangiectasia

For Hereditary hemorrhagic telangiectasia (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ENG p.Asp365Asn Benign/Likely benign ★★ same residue
ENG p.Asp365Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
ENG p.Asp365Tyr Uncertain significance ★ ⚠ same residue
ENG p.Asp365Gly Uncertain significance ★ ⚠ same residue
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

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-asp365 (accessed [today's date]).

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