Is NF1 p.Gln2002= (c.6006G>A) pathogenic?

NF1 p.Gln2002= (c.6006G>A) is classified Pathogenic/Likely pathogenic in NF1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-12-03). Very rare (popmax 8.48e-05%, nfe); Associated with neurofibromatosis type 1.

What condition is associated with NF1 p.Gln2002= (c.6006G>A)?

NF1 p.Gln2002= (c.6006G>A) is associated with neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Gln2002= (c.6006G>A) in the general population?

NF1 p.Gln2002= (c.6006G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Neurofibromatosis type 1 inherited?

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

NF1 p.Gln2002=

c.6006G>A · rs1555534432 · VCV1298697

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

neurofibromatosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.94	donor loss · deltas
Pangolin	Δ0.82	loss · gain 0.80 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,120 alleles

Overall 6.21e-05% 1/1,611,154 alleles · very rare exomes 0/1,460,416 · genomes 1/150,738 · joint denominator

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: NF1
Protein: p.Gln2002=
Coding: c.6006G>A
MANE Select: NM_001042492
dbSNP: rs1555534432
Type: single nucleotide variant
Location: chr17:31335031 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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.Gln2002Ter Pathogenic ★★ same residue
NF1 p.Gln2002Pro Uncertain significance ★★ ⚠ same residue
NF1 p.Gln2002His Conflicting classifications of pathogenicity ★ ⚠ same residue
NF1 p.Gln2002fs Pathogenic same residue
NF1 c.1062+1G>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+1G>C Pathogenic ★★ same condition
NF1 c.1062+2T>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+2T>C 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-gln2002 (accessed [today's date]).

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