Is NEBL p.Asp895= (c.2685C>T) pathogenic?

NEBL p.Asp895= (c.2685C>T) is classified Benign/Likely benign in NEBL (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-31). Rare (popmax 0.475%, afr); Associated with dilated cardiomyopathy.

What condition is associated with NEBL p.Asp895= (c.2685C>T)?

NEBL p.Asp895= (c.2685C>T) is associated with dilated cardiomyopathy (ClinVar).

How common is NEBL p.Asp895= (c.2685C>T) in the general population?

NEBL p.Asp895= (c.2685C>T) is rare (popmax 0.475%, afr) (gnomAD).

NEBL p.Asp895=

c.2685C>T · rs140245727 · VCV178093

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.475%, afr)

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.088	GERP -5.2, phastCons 0.007
Overall
CADD	6.875	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.475% African / African-American · 356/74,964 alleles

Filtering AF 0.434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.418%

Overall 0.0264% 426/1,613,358 alleles · rare exomes 236/1,461,210 · genomes 190/152,148 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.475%	211
South Asian	0.0307%	3,252
Remaining individualsnot grpmax-eligible	0.024%	4,166
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,918
Admixed American	0.0117%	8,571
East Asian	0.00446%	22,428
European (non-Finnish)	0.0011%	90,726

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.Asp895=
Coding: c.2685C>T
MANE Select: NM_006393
dbSNP: rs140245727
Type: single nucleotide variant
Location: chr10:20808586 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB
Residue 895: 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.Asp895Ala 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-asp895 (accessed [today's date]).

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