Is NF1 p.Ser2152= (c.6456T>C) pathogenic?

NF1 p.Ser2152= (c.6456T>C) is classified Benign/Likely benign in NF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-21). Very rare (popmax 0.00446%, eas); Associated with neurofibromatosis type 1.

What condition is associated with NF1 p.Ser2152= (c.6456T>C)?

NF1 p.Ser2152= (c.6456T>C) is associated with neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Ser2152= (c.6456T>C) in the general population?

NF1 p.Ser2152= (c.6456T>C) is very rare (popmax 0.00446%, eas) (gnomAD).

How is Neurofibromatosis type 1 inherited?

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

NF1 p.Ser2152=

c.6456T>C · rs776897972 · VCV413005

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

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 0.67	GERP 1.7, phastCons 1
Overall
CADD	8.289	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,884 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,614,132 alleles · very rare exomes 2/1,461,762 · genomes 0/152,370 · 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.Ser2152=
Coding: c.6456T>C
MANE Select: NM_001042492
dbSNP: rs776897972
Type: single nucleotide variant
Location: chr17:31337396 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2152: 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

For Neurofibromatosis type 1 (Orphanet):

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

Similar variants

NF1 p.Ser2152Gly Uncertain significance ★★ same residue
NF1 p.Ser2152fs 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
NF1 c.1062+3A>G Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+3A>T 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-ser2152 (accessed [today's date]).

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