Is NEXN p.Pro244= (c.732C>A) pathogenic?

NEXN p.Pro244= (c.732C>A) is classified Benign/Likely benign in NEXN (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0655%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with NEXN p.Pro244= (c.732C>A)?

NEXN p.Pro244= (c.732C>A) is associated with Cardiovascular phenotype, cardiomyopathy, dilated cardiomyopathy 1CC (ClinVar).

How common is NEXN p.Pro244= (c.732C>A) in the general population?

NEXN p.Pro244= (c.732C>A) is ultra-rare (popmax 0.0655%, nfe) (gnomAD).

NEXN p.Pro244=

c.732C>A · rs201171783 · VCV47910

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0655%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.265	benign-leaning
Splicing
SpliceAI	Δ0.30	acceptor gain · deltas
Pangolin	Δ0.29	gain · loss 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.4	GERP 0.93, phastCons 1
Overall
CADD	15.66	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0655% European (non-Finnish) · 773/1,179,922 alleles

Filtering AF 0.0617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0601%

Overall 0.0632% 1,020/1,613,402 alleles · ultra-rare exomes 946/1,461,572 · genomes 74/151,830 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.635%	157
European (non-Finnish)grpmax	0.0655%	1,526
Remaining individualsnot grpmax-eligible	0.0608%	1,644
Finnishnot grpmax-eligible	0.0125%	7,993
African / African-American	0.00937%	10,676
Admixed American	0.00835%	11,981
East Asian	0.00223%	44,850

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro244=
Coding: c.732C>A
MANE Select: NM_144573
dbSNP: rs201171783
Type: single nucleotide variant
Location: chr1:77926760 (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.Pro244Ser 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
NEXN c.-10T>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-pro244 (accessed [today's date]).

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