Is ENG p.Gln489fs (c.1465_1466del) pathogenic?

ENG p.Gln489fs (c.14651466del) is classified Pathogenic in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). Absent from gnomAD; Associated with Cardiovascular phenotype.

What condition is associated with ENG p.Gln489fs (c.1465_1466del)?

ENG p.Gln489fs (c.1465_1466del) is associated with Cardiovascular phenotype (ClinVar).

How common is ENG p.Gln489fs (c.1465_1466del) in the general population?

ENG p.Gln489fs (c.1465_1466del) is absent from gnomAD (gnomAD).

ENG p.Gln489fs

c.1465_1466del · rs2539059836 · VCV1773227

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.2	GERP 0.54, phastCons 0.062

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.Gln489fs
Coding: c.1465_1466del
MANE Select: NM_001114753
dbSNP: rs2539059836
Type: Deletion
Location: chr9:127818340 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 489: a β-strand; the zp domain

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.Arg232_Thr233del Likely pathogenic ★★ same condition
ENG p.Asp578fs Pathogenic/Likely pathogenic ★★ same condition
ENG p.Gln33fs Pathogenic ★★ same condition
ENG p.Gln489Ter Pathogenic/Likely pathogenic ★★ same residue
ENG p.Gly413fs Pathogenic ★★ same condition
ENG p.Gly514fs Pathogenic ★★ same condition
ENG p.Ile263del Pathogenic/Likely pathogenic ★★ same condition
ENG p.Leu299fs Pathogenic/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-gln489fs (accessed [today's date]).

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