Is NF1 p.Ser2467Ter (c.7400C>G) pathogenic?

NF1 p.Ser2467Ter (c.7400C>G) is classified Pathogenic in NF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-01). Very rare (popmax 6.2e-05%); Associated with neurofibromatosis type 1.

What condition is associated with NF1 p.Ser2467Ter (c.7400C>G)?

NF1 p.Ser2467Ter (c.7400C>G) is associated with neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Ser2467Ter (c.7400C>G) in the general population?

NF1 p.Ser2467Ter (c.7400C>G) is very rare (popmax 6.2e-05%) (gnomAD).

How is Neurofibromatosis type 1 inherited?

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

NF1 p.Ser2467Ter

c.7400C>G · rs1555536135 · VCV2138002

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

neurofibromatosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 50 of 58
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,526 alleles · very rare exomes 1/1,461,240 · genomes 0/152,286 · 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.Ser2467Ter
Coding: c.7400C>G
MANE Select: NM_001042492
dbSNP: rs1555536135
Type: single nucleotide variant
Location: chr17:31350261 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2467: a modified residue (phosphoserine)

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.Ser2467Leu Uncertain significance ★★ ⚠ same residue
NF1 p.Ser2467Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
NF1 p.Ser2467= Likely benign ★ same residue
NF1 p.Ser2467fs 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-ser2467ter (accessed [today's date]).

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