Is NF1 p.Pro2483= (c.7449T>C) pathogenic?

NF1 p.Pro2483= (c.7449T>C) is classified Benign/Likely benign in NF1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-21). Ultra-rare (popmax 0.0164%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with NF1 p.Pro2483= (c.7449T>C)?

NF1 p.Pro2483= (c.7449T>C) is associated with hereditary neoplastic syndrome, neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Pro2483= (c.7449T>C) in the general population?

NF1 p.Pro2483= (c.7449T>C) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

NF1 p.Pro2483=

c.7449T>C · rs878853916 · VCV237595

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

hereditary neoplastic syndrome

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 -0.33	GERP -3.4, phastCons 0.2
Overall
CADD	4.005	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,612,192 alleles · ultra-rare exomes 8/1,459,972 · genomes 1/152,220 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.0032%	31,208
European (non-Finnish)	0.000509%	196,451

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.Pro2483=
Coding: c.7449T>C
MANE Select: NM_001042492
dbSNP: rs878853916
Type: single nucleotide variant
Location: chr17:31350310 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurofibromatosis type 1

Similar variants

NF1 p.Pro2483Arg Uncertain significance ★★ ⚠ same residue
NF1 p.Pro2483Leu Uncertain significance ★ ⚠ same residue
NF1 p.Pro2483Ser Conflicting classifications of pathogenicity ★ ⚠ 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
NF1 c.1062+3A>G 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-pro2483 (accessed [today's date]).

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