Is ENG p.Ser328Ter (c.983_984delinsAG) pathogenic?

ENG p.Ser328Ter (c.983984delinsAG) is classified Pathogenic in ENG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-30). Absent from gnomAD; Associated with hereditary hemorrhagic telangiectasia.

What condition is associated with ENG p.Ser328Ter (c.983_984delinsAG)?

ENG p.Ser328Ter (c.983_984delinsAG) is associated with hereditary hemorrhagic telangiectasia (ClinVar).

How common is ENG p.Ser328Ter (c.983_984delinsAG) in the general population?

ENG p.Ser328Ter (c.983_984delinsAG) is absent from gnomAD (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

ENG p.Ser328Ter

c.983_984delinsAG · rs1588581338 · VCV665098

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary hemorrhagic telangiectasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 7 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.8	GERP -0.68, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ENG
Protein: p.Ser328Ter
Coding: c.983_984delinsAG
MANE Select: NM_001114753
dbSNP: rs1588581338
Type: Indel
Location: chr9:127824807 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 328: a disulfide bond; the 'required for interaction with gdf2' region; the 'or1, c-terminal part' region

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.Ser328fs Pathogenic ★ same residue
ENG p.Ser328Thr Uncertain significance ★ ⚠ same residue
ENG p.Lys374Ser Pathogenic/Likely pathogenic ★★ same condition
ENG p.Thr344fs Pathogenic ★★ same condition
ENG p.Ala60Glu Benign/Likely benign ★★ same condition
ENG c.1135-3_1135-2delinsAG Likely pathogenic ★ same condition
ENG p.Lys291fs Pathogenic ★ same condition
ENG p.Tyr258fs 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-ser328ter (accessed [today's date]).

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