Is NEXN p.Pro244Ser (c.730C>T) pathogenic?

NEXN p.Pro244Ser (c.730C>T) is classified Uncertain significance in NEXN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-27). AlphaMissense: likely benign (0.1759); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with NEXN p.Pro244Ser (c.730C>T)?

NEXN p.Pro244Ser (c.730C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1CC, hypertrophic cardiomyopathy 20 (ClinVar).

How common is NEXN p.Pro244Ser (c.730C>T) in the general population?

NEXN p.Pro244Ser (c.730C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NEXN p.Pro244Ser (c.730C>T)?

AlphaMissense predicts likely benign (score 0.1759) — an in-silico prediction, not a clinical call.

NEXN p.Pro244Ser

c.730C>T · rs1054602820 · VCV2079125

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1759 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1759	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -8.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.35	constrained · MANE · 85 bp · p 0.00047 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro244Ser
Coding: c.730C>T
MANE Select: NM_144573
dbSNP: rs1054602820
Type: single nucleotide variant
Location: chr1:77926758 (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.Pro244= Benign/Likely benign ★★ 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.-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-pro244ser (accessed [today's date]).

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