Is ENG p.Gln335Ter (c.1002_1003delinsCT) pathogenic?

ENG p.Gln335Ter (c.10021003delinsCT) is classified Pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Absent from gnomAD; Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Gln335Ter (c.1002_1003delinsCT)?

ENG p.Gln335Ter (c.1002_1003delinsCT) is associated with Cardiovascular phenotype (ClinVar).

How common is ENG p.Gln335Ter (c.1002_1003delinsCT) in the general population?

ENG p.Gln335Ter (c.1002_1003delinsCT) is absent from gnomAD (gnomAD).

ENG p.Gln335Ter

c.1002_1003delinsCT · rs2539071301 · VCV1770012

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

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 8 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 1.6, 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.Gln335Ter
Coding: c.1002_1003delinsCT
MANE Select: NM_001114753
dbSNP: rs2539071301
Type: Indel
Location: chr9:127824435 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 335: the 'required for interaction with gdf2' region

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

Similar variants

ENG p.Lys374Ser Pathogenic/Likely pathogenic ★★ same condition
ENG p.Ala60Glu Benign/Likely benign ★★ same condition
ENG p.Ala151fs Pathogenic ★ same condition
ENG p.Asp496fs Pathogenic ★ same condition
ENG p.Ala418_Met420delinsTyr Uncertain significance ★ same condition
ENG p.Ser548_Val551delinsThrAlaAla Uncertain significance ★ same condition
ENG c.1134+1G>T Pathogenic/Likely pathogenic ★★ same condition
ENG c.1311+2T>A 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-gln335ter (accessed [today's date]).

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