Is NEBL p.Phe975fs (c.2923_2980del) pathogenic?

NEBL p.Phe975fs (c.29232980del) is classified Uncertain significance in NEBL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Phe975fs (c.2923_2980del)?

NEBL p.Phe975fs (c.2923_2980del) is associated with dilated cardiomyopathy (ClinVar).

NEBL p.Phe975fs

c.2923_2980del · VCV3727398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (28 of 28) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1

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

Variant & gene context

Gene: NEBL
Protein: p.Phe975fs
Coding: c.2923_2980del
MANE Select: NM_006393
Type: Deletion
Location: chr10:20785812 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB
Residue 975: the sh3 domain

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

Disease context

dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NEBL p.Asn23_Glu24del Uncertain significance ★★ same condition
NEBL p.Asn346fs Uncertain significance ★★ same condition
NEBL p.Gly81fs Uncertain significance ★★ same condition
NEBL p.Ile456fs Uncertain significance ★★ same condition
NEBL p.Ile93fs Uncertain significance ★★ same condition
NEBL p.Leu37fs Uncertain significance ★★ same condition
NEBL c.2519-2del Benign ★★ same condition
NEBL c.357+73457del Benign ★★ 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/nebl-p-phe975fs (accessed [today's date]).

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