Is NEXN p.Ile150= (c.450T>A) pathogenic?

NEXN p.Ile150= (c.450T>A) is classified Conflicting classifications of pathogenicity in NEXN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-06). Very rare (popmax 0.000172%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with NEXN p.Ile150= (c.450T>A)?

NEXN p.Ile150= (c.450T>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1CC, hypertrophic cardiomyopathy 20 (ClinVar).

How common is NEXN p.Ile150= (c.450T>A) in the general population?

NEXN p.Ile150= (c.450T>A) is very rare (popmax 0.000172%, nfe) (gnomAD).

NEXN p.Ile150=

c.450T>A · rs1064797051 · VCV424583

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000172%, nfe)

Conditions

Cardiovascular phenotype

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 · T>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 2.1, phastCons 1
Overall
CADD	16.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000172% European (non-Finnish) · 2/1,163,952 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,593,932 alleles · very rare exomes 2/1,441,634 · genomes 0/152,298 · joint denominator

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.Ile150=
Coding: c.450T>A
MANE Select: NM_144573
dbSNP: rs1064797051
Type: single nucleotide variant
Location: chr1:77925190 (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: dilated cardiomyopathy 1CC hypertrophic cardiomyopathy 20

Similar variants

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.-10T>C Uncertain significance ★★ same condition
NEXN p.Ala266Gly Uncertain significance ★★ ⚠ same condition
NEXN p.Ala343Val 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-ile150 (accessed [today's date]).

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