Is NEXN p.Asp52= (c.156C>T) pathogenic?

NEXN p.Asp52= (c.156C>T) is classified Benign/Likely benign in NEXN (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-19). Rare (popmax 0.413%, afr); Associated with dilated cardiomyopathy 1CC.

What condition is associated with NEXN p.Asp52= (c.156C>T)?

NEXN p.Asp52= (c.156C>T) is associated with dilated cardiomyopathy 1CC, cardiomyopathy, hypertrophic cardiomyopathy 20 (ClinVar).

How common is NEXN p.Asp52= (c.156C>T) in the general population?

NEXN p.Asp52= (c.156C>T) is rare (popmax 0.413%, afr) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NEXN p.Asp52=

c.156C>T · rs371431782 · VCV226849

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.413%, afr)

Conditions

dilated cardiomyopathy 1CC

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 -4.9	GERP -3.8
Overall
CADD	6.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.413% African / African-American · 308/74,602 alleles

Filtering AF 0.375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.36%

Overall 0.0231% 372/1,610,948 alleles · rare exomes 197/1,459,524 · genomes 175/151,424 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.413%	242
Remaining individualsnot grpmax-eligible	0.0224%	4,458
Admixed American	0.0184%	5,427
Middle Eastern	0.0165%	6,046
South Asian	0.00331%	30,224
Finnishnot grpmax-eligible	0.00313%	31,918
European (non-Finnish)	0.00272%	36,828
East Asian	0.00223%	44,746

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: NEXN
Protein: p.Asp52=
Coding: c.156C>T
MANE Select: NM_144573
dbSNP: rs371431782
Type: single nucleotide variant
Location: chr1:77917694 (GRCh38)
Gene constraint: LOEUF 0.878 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.78
Residue 52: the 'disordered' region; a UniProt-annotated variant site (in cmh20; uncertain significance)

Full NEXN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1CC — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy hypertrophic cardiomyopathy 20

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

NEXN p.Asp52Glu Uncertain significance ★ ⚠ same residue
NEXN p.Gly100Ter Pathogenic ★★ same condition
NEXN c.1473+1G>T Uncertain significance ★★ same condition
NEXN c.219+5T>G Uncertain significance ★★ same condition
NEXN c.299-3T>C Uncertain significance ★★ same condition
NEXN c.865-4T>C Uncertain significance ★★ same condition
NEXN c.-10T>C Uncertain significance ★★ same condition
NEXN p.Ala266Gly 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/nexn-p-asp52 (accessed [today's date]).

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