Is NEXN p.Val18= (c.54C>A) pathogenic?

NEXN p.Val18= (c.54C>A) is classified Likely benign in NEXN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with NEXN p.Val18= (c.54C>A)?

NEXN p.Val18= (c.54C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is NEXN p.Val18= (c.54C>A) in the general population?

NEXN p.Val18= (c.54C>A) is absent from gnomAD v4.1 (gnomAD).

NEXN p.Val18=

c.54C>A · VCV3404561

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

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 0.35	GERP 0.42, phastCons 0.98
Overall
CADD	6.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NEXN
Protein: p.Val18=
Coding: c.54C>A
MANE Select: NM_144573
Type: single nucleotide variant
Location: chr1:77917592 (GRCh38)
Gene constraint: LOEUF 0.878 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.78
Residue 18: the 'disordered' region

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

Similar variants

NEXN p.Val18Ile Uncertain significance ★★ ⚠ same residue
NEXN p.Val18Ala Uncertain significance ★ same residue
NEXN c.448-4A>G Uncertain significance ★★ same condition
NEXN p.Ala266Gly Uncertain significance ★★ ⚠ same condition
NEXN p.Ala343Val Uncertain significance ★★ ⚠ same condition
NEXN p.Ala476Thr Uncertain significance ★★ ⚠ same condition
NEXN p.Ala486Gly Uncertain significance ★★ ⚠ same condition
NEXN p.Ala500Ser 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-val18 (accessed [today's date]).

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