Is NEXN p.Ile613= (c.1839T>A) pathogenic?

NEXN p.Ile613= (c.1839T>A) is classified Likely benign in NEXN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-10). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with NEXN p.Ile613= (c.1839T>A)?

NEXN p.Ile613= (c.1839T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is NEXN p.Ile613= (c.1839T>A) in the general population?

NEXN p.Ile613= (c.1839T>A) is absent from gnomAD v4.1 (gnomAD).

NEXN p.Ile613=

c.1839T>A · rs2523310809 · VCV1781099

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 -1.5	GERP -4.6
Overall
CADD	1.025	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.Ile613=
Coding: c.1839T>A
MANE Select: NM_144573
dbSNP: rs2523310809
Type: single nucleotide variant
Location: chr1:77942640 (GRCh38)
Gene constraint: LOEUF 0.878 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.78
Residue 613: the ig-like domain; a UniProt-annotated variant site (in cmd2m; likely pathogenic)

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 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
NEXN p.Ala500Thr Uncertain significance ★★ ⚠ same condition
NEXN p.Arg127Cys 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-ile613 (accessed [today's date]).

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