Is NF1 p.Ser1355fs (c.4062_4078del) pathogenic?

NF1 p.Ser1355fs (c.40624078del) is classified Pathogenic in NF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-06). No gnomAD frequency available for this variant; Associated with neurofibromatosis type 1.

What condition is associated with NF1 p.Ser1355fs (c.4062_4078del)?

NF1 p.Ser1355fs (c.4062_4078del) is associated with neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Ser1355fs (c.4062_4078del) in the general population?

NF1 p.Ser1355fs (c.4062_4078del) is no gnomAD frequency available for this variant (gnomAD).

How is Neurofibromatosis type 1 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

NF1 p.Ser1355fs

c.4062_4078del · rs2508352015 · VCV2076532

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neurofibromatosis type 1

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 30 of 58
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NF1
Protein: p.Ser1355fs
Coding: c.4062_4078del
MANE Select: NM_001042492
dbSNP: rs2508352015
Type: Deletion
Location: chr17:31249067 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1355: an α-helix; the ras-gap domain

Full NF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurofibromatosis type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Neurofibromatosis type 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: 1-5 / 10 000 (United Kingdom)

Similar variants

NF1 p.Ser1355= Likely benign ★★ same residue
NF1 p.Ser1355Ter Pathogenic ★ same residue
NF1 c.1183_1185+2del Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1392+2del Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1527+1del Pathogenic ★★ same condition
NF1 c.1527+4_1527+7del Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1845+1_1845+5del Pathogenic ★★ same condition
NF1 c.2002-2_2002-1del Pathogenic/Likely 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-ser1355fs (accessed [today's date]).

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