Is NF1 p.Arg752fs (c.2253_2254dup) pathogenic?

NF1 p.Arg752fs (c.22532254dup) is classified Pathogenic in NF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-11). Associated with Cardiovascular phenotype.

What condition is associated with NF1 p.Arg752fs (c.2253_2254dup)?

NF1 p.Arg752fs (c.2253_2254dup) is associated with Cardiovascular phenotype, hereditary neoplastic syndrome (ClinVar).

NF1 p.Arg752fs

c.2253_2254dup · VCV3879055

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 19 of 58
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: NF1
Protein: p.Arg752fs
Coding: c.2253_2254dup
MANE Select: NM_001042492
Type: Duplication
Location: chr17:31227218 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 752: an α-helix

Full NF1 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: hereditary neoplastic syndrome

Similar variants

NF1 p.Arg752Ser Uncertain significance ★★ same residue
NF1 p.Arg752Ter Pathogenic ★ same residue
NF1 p.Arg752Thr Uncertain significance ★ same residue
NF1 c.288+1dup Pathogenic/Likely pathogenic ★★ same condition
NF1 c.654+2dup Pathogenic/Likely pathogenic ★★ same condition
NF1 p.Ala1530fs Pathogenic ★★ same condition
NF1 p.Ala219fs Pathogenic ★★ same condition
NF1 p.Ala264fs Pathogenic ★★ 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/nf1-p-arg752fs (accessed [today's date]).

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