Is NEXN p.Asp355= (c.1065T>C) pathogenic?

NEXN p.Asp355= (c.1065T>C) is classified Benign/Likely benign in NEXN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-27). Rare (popmax 0.138%, sas); Associated with Cardiovascular phenotype.

What condition is associated with NEXN p.Asp355= (c.1065T>C)?

NEXN p.Asp355= (c.1065T>C) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1CC (ClinVar).

How common is NEXN p.Asp355= (c.1065T>C) in the general population?

NEXN p.Asp355= (c.1065T>C) is rare (popmax 0.138%, sas) (gnomAD).

NEXN p.Asp355=

c.1065T>C · rs369897647 · VCV164790

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.138%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.052	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -4.3, phastCons 0.17
Overall
CADD	8.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.138% South Asian · 124/90,036 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.0152% 242/1,590,534 alleles · rare exomes 232/1,438,208 · genomes 10/152,326 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.138%	726
Remaining individualsnot grpmax-eligible	0.0292%	3,423
Admixed American	0.0268%	3,732
European (non-Finnish)	0.00724%	13,816

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.Asp355=
Coding: c.1065T>C
MANE Select: NM_144573
dbSNP: rs369897647
Type: single nucleotide variant
Location: chr1:77933293 (GRCh38)
Gene constraint: LOEUF 0.878 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.78

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy dilated cardiomyopathy 1CC hypertrophic cardiomyopathy 20

Similar variants

NEXN p.Asp355Gly Uncertain significance ★ ⚠ same residue
NEXN p.Asp355His 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.448-4A>G Uncertain significance ★★ same condition
NEXN c.865-4T>C 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-asp355 (accessed [today's date]).

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