Is NEBL p.Asp467Glu (c.1401C>G) pathogenic?

NEBL p.Asp467Glu (c.1401C>G) is classified Uncertain significance in NEBL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-21). AlphaMissense: likely benign (0.236); Very rare (popmax 8.48e-05%, nfe); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Asp467Glu (c.1401C>G)?

NEBL p.Asp467Glu (c.1401C>G) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Asp467Glu (c.1401C>G) in the general population?

NEBL p.Asp467Glu (c.1401C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about NEBL p.Asp467Glu (c.1401C>G)?

AlphaMissense predicts likely benign (score 0.236) — an in-silico prediction, not a clinical call.

NEBL p.Asp467Glu

c.1401C>G · rs769479569 · VCV583115

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.236 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.236	likely benign
REVEL	0.135	moderately benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.029	GERP -1.9, phastCons 0.002
Regional constraint	o/e 1.15	unconstrained · MANE · 111 kb · p 7.4e-07 · regional, not allelic
Overall
CADD	6.625	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,922 alleles

Overall 6.2e-05% 1/1,612,786 alleles · very rare exomes 1/1,460,488 · genomes 0/152,298 · joint denominator

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.Asp467Glu
Coding: c.1401C>G
MANE Select: NM_006393
dbSNP: rs769479569
Type: single nucleotide variant
Location: chr10:20835561 (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

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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
NEBL p.Ala440Asp 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-asp467glu (accessed [today's date]).

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