Is NF1 p.Phe1247= (c.3741T>C) pathogenic?

NF1 p.Phe1247= (c.3741T>C) is classified Likely benign in NF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-02). Very rare (popmax 0.0011%, sas); Associated with neurofibromatosis type 1.

What condition is associated with NF1 p.Phe1247= (c.3741T>C)?

NF1 p.Phe1247= (c.3741T>C) is associated with neurofibromatosis type 1, hereditary neoplastic syndrome (ClinVar).

How common is NF1 p.Phe1247= (c.3741T>C) in the general population?

NF1 p.Phe1247= (c.3741T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Neurofibromatosis type 1 inherited?

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

NF1 p.Phe1247=

c.3741T>C · rs1049357346 · VCV2809489

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

neurofibromatosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.76, phastCons 1
Overall
CADD	10.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 6.2e-05% 1/1,614,182 alleles · very rare exomes 1/1,461,822 · genomes 0/152,360 · 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.Phe1247=
Coding: c.3741T>C
MANE Select: NM_001042492
dbSNP: rs1049357346
Type: single nucleotide variant
Location: chr17:31235643 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1247: an α-helix

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

Also linked: hereditary neoplastic syndrome

For Neurofibromatosis type 1 (Orphanet):

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

Similar variants

NF1 p.Phe1247Leu Uncertain significance ★★ ⚠ same residue
NF1 p.Phe1247Cys Uncertain significance ★ ⚠ same residue
NF1 p.Phe1247fs Pathogenic ★ same residue
NF1 p.Phe1247Ile Likely 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-phe1247 (accessed [today's date]).

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