Is NEBL p.Arg882Ter (c.2644C>T) pathogenic?

NEBL p.Arg882Ter (c.2644C>T) is classified Uncertain significance in NEBL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-16). Very rare (popmax 0.00892%, eas); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Arg882Ter (c.2644C>T)?

NEBL p.Arg882Ter (c.2644C>T) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Arg882Ter (c.2644C>T) in the general population?

NEBL p.Arg882Ter (c.2644C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

NEBL p.Arg882Ter

c.2644C>T · rs151012132 · VCV201910

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Conditions

dilated cardiomyopathy

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
NMD	predicted	premature termination codon in exon 26 of 28
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,848 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00155% 25/1,613,356 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,212
European (non-Finnish)	0.00161%	62,075
Remaining individualsnot grpmax-eligible	0.0016%	62,476
African / African-American	0.00133%	74,976

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: NEBL
Protein: p.Arg882Ter
Coding: c.2644C>T
MANE Select: NM_006393
dbSNP: rs151012132
Type: single nucleotide variant
Location: chr10:20808627 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB
Residue 882: the 'linker' region

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.Arg882Gln Uncertain significance ★★ ⚠ same residue
NEBL p.Arg882Leu Uncertain significance ★★ ⚠ same residue
NEBL c.1227+5G>A Uncertain significance ★★ same condition
NEBL c.1870-1G>A Uncertain significance ★★ same condition
NEBL c.798+1G>A Uncertain significance ★★ same condition
NEBL c.903+1G>T Uncertain significance ★★ same condition
NEBL p.Ala114Ser Uncertain significance ★★ ⚠ same condition
NEBL p.Ala219Thr Uncertain significance ★★ ⚠ 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-arg882ter (accessed [today's date]).

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