Is ENG p.Asp366= (c.1098C>T) pathogenic?

ENG p.Asp366= (c.1098C>T) is classified Conflicting classifications of pathogenicity in ENG (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-31). Rare (popmax 0.23%, eas); Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Asp366= (c.1098C>T)?

ENG p.Asp366= (c.1098C>T) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 1, hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Asp366= (c.1098C>T) in the general population?

ENG p.Asp366= (c.1098C>T) is rare (popmax 0.23%, eas) (gnomAD).

ENG p.Asp366=

c.1098C>T · rs201497772 · VCV414307

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.23%, eas)

Conditions

Cardiovascular phenotype

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 -0.27	GERP -2.8
Overall
CADD	3.698	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.23% East Asian · 103/44,858 alleles

Filtering AF 0.194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.18%

Overall 0.00799% 129/1,613,984 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.23%	436
Remaining individualsnot grpmax-eligible	0.0032%	31,252
European (non-Finnish)	0.00195%	51,305
Admixed American	0.00167%	59,986

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.Asp366=
Coding: c.1098C>T
MANE Select: NM_001114753
dbSNP: rs201497772
Type: single nucleotide variant
Location: chr9:127824340 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 366: a β-strand; a disulfide bond; the zp domain; a UniProt-annotated variant site (in)

Full ENG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: telangiectasia, hereditary hemorrhagic, type 1 hereditary hemorrhagic telangiectasia

Similar variants

ENG p.Asp366His Benign/Likely benign ★★ same residue
ENG p.Asp366Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
ENG p.Asp366Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ENG p.Asp366_Ala367insTer Pathogenic ★ same residue
ENG p.Asp366fs Pathogenic ★ same residue
ENG p.Asp366_Ala367insAsp Uncertain significance ★ same residue
ENG p.Arg529His Pathogenic ★★★ ⚠ same condition
ENG p.Asn423Ser 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-asp366 (accessed [today's date]).

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