Is NF1 p.Pro2477Ser (c.7429C>T) pathogenic?

NF1 p.Pro2477Ser (c.7429C>T) is classified Uncertain significance in NF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-02). AlphaMissense: likely benign (0.0672); Absent from gnomAD v4.1; Associated with juvenile myelomonocytic leukemia.

What condition is associated with NF1 p.Pro2477Ser (c.7429C>T)?

NF1 p.Pro2477Ser (c.7429C>T) is associated with juvenile myelomonocytic leukemia, neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Pro2477Ser (c.7429C>T) in the general population?

NF1 p.Pro2477Ser (c.7429C>T) is absent from gnomAD v4.1 (gnomAD).

How is Juvenile myelomonocytic leukemia inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about NF1 p.Pro2477Ser (c.7429C>T)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

NF1 p.Pro2477Ser

c.7429C>T · rs876658722 · VCV954665

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

juvenile myelomonocytic leukemia

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.063, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 37 kb · p 1.1e-16 · regional, not allelic
Overall
CADD	15.59	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NF1
Protein: p.Pro2477Ser
Coding: c.7429C>T
MANE Select: NM_001042492
dbSNP: rs876658722
Type: single nucleotide variant
Location: chr17:31350290 (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

juvenile myelomonocytic leukemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurofibromatosis type 1

For Juvenile myelomonocytic leukemia (Orphanet):

Inheritance: Not applicable
Onset: Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

NF1 p.Pro2477Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
NF1 p.Pro2477= Likely benign ★ same residue
NF1 p.Pro2477His Likely benign ★ same residue
NF1 p.Pro2477Leu Likely benign ★ 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-pro2477ser (accessed [today's date]).

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