Is NEBL p.Ser746= (c.2238C>T) pathogenic?

NEBL p.Ser746= (c.2238C>T) is classified Likely benign in NEBL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). Very rare (popmax 0.00223%, eas); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Ser746= (c.2238C>T)?

NEBL p.Ser746= (c.2238C>T) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Ser746= (c.2238C>T) in the general population?

NEBL p.Ser746= (c.2238C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

NEBL p.Ser746=

c.2238C>T · VCV4737685

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.81 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.8	GERP -0.37, phastCons 1
Overall
CADD	10.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,760 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000207% 3/1,450,930 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,760
European (non-Finnish)	0.000171%	585,134

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.Ser746=
Coding: c.2238C>T
MANE Select: NM_006393
Type: single nucleotide variant
Location: chr10:20815628 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB

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.Ser746Thr 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
NEBL p.Ala264Val 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-ser746 (accessed [today's date]).

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