Is NEBL p.Val5Ala (c.14T>C) pathogenic?

NEBL p.Val5Ala (c.14T>C) is classified Uncertain significance in NEBL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-24). AlphaMissense: likely benign (0.1245); Ultra-rare (popmax 0.0617%, afr); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Val5Ala (c.14T>C)?

NEBL p.Val5Ala (c.14T>C) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Val5Ala (c.14T>C) in the general population?

NEBL p.Val5Ala (c.14T>C) is ultra-rare (popmax 0.0617%, afr) (gnomAD).

What do computational predictors say about NEBL p.Val5Ala (c.14T>C)?

AlphaMissense predicts likely benign (score 0.1245) — an in-silico prediction, not a clinical call.

NEBL p.Val5Ala

c.14T>C · rs145770601 · VCV45481

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1245 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.1245	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -7.17	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 1.2	GERP 1.2
Regional constraint	o/e 1.15	unconstrained · MANE · 111 kb · p 7.4e-07 · regional, not allelic
Overall
CADD	14.31	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 0.0617% African / African-American · 46/74,552 alleles

Filtering AF 0.0474% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0425%

Overall 0.00338% 54/1,599,238 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0617%	1,621
Middle Eastern	0.0166%	6,020
Admixed American	0.00682%	14,664
Remaining individualsnot grpmax-eligible	0.00484%	20,647

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.Val5Ala
Coding: c.14T>C
MANE Select: NM_006393
dbSNP: rs145770601
Type: single nucleotide variant
Location: chr10:20897192 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB
Residue 5: the 'disordered' 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.Val5Ile 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-val5ala (accessed [today's date]).

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