Is NEBL p.Ala873= (c.2619G>A) pathogenic?

NEBL p.Ala873= (c.2619G>A) is classified Likely benign in NEBL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-12). Ultra-rare (popmax 0.035%, amr); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Ala873= (c.2619G>A)?

NEBL p.Ala873= (c.2619G>A) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Ala873= (c.2619G>A) in the general population?

NEBL p.Ala873= (c.2619G>A) is ultra-rare (popmax 0.035%, amr) (gnomAD).

NEBL p.Ala873=

c.2619G>A · rs140803920 · VCV383206

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

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 · C>A here scores Δ0.32 · evaluated, not missing
Pangolin	Δ0.20	loss · gain 0.00 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP -6.7	GERP -5.2
Overall
CADD	4.111	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.035% Admixed American · 21/59,986 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00992% 160/1,612,630 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,856
European (non-Finnish)	0.0112%	8,931
Remaining individualsnot grpmax-eligible	0.0048%	20,820
East Asian	0.00223%	44,850
South Asian	0.0022%	45,510
African / African-American	0.00133%	74,926

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.Ala873=
Coding: c.2619G>A
MANE Select: NM_006393
dbSNP: rs140803920
Type: single nucleotide variant
Location: chr10:20808652 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB
Residue 873: 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.Ala873Val 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-ala873 (accessed [today's date]).

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