Is NF1 p.Val207Phe (c.619G>T) pathogenic?

NF1 p.Val207Phe (c.619G>T) is classified Uncertain significance in NF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-04). AlphaMissense: likely benign (0.2946); Absent from gnomAD v4.1; Associated with juvenile myelomonocytic leukemia.

What condition is associated with NF1 p.Val207Phe (c.619G>T)?

NF1 p.Val207Phe (c.619G>T) is associated with juvenile myelomonocytic leukemia (ClinVar).

How common is NF1 p.Val207Phe (c.619G>T) in the general population?

NF1 p.Val207Phe (c.619G>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.Val207Phe (c.619G>T)?

AlphaMissense predicts likely benign (score 0.2946) — an in-silico prediction, not a clinical call.

NF1 p.Val207Phe

c.619G>T · rs752959118 · VCV2677180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2946 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

juvenile myelomonocytic leukemia

Computational evidence

Protein change
AlphaMissense	0.2946	likely benign
REVEL	0.396	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP -0.065, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 87 kb · p 4.8e-08 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

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.Val207Phe
Coding: c.619G>T
MANE Select: NM_001042492
dbSNP: rs752959118
Type: single nucleotide variant
Location: chr17:31181454 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 207: an α-helix

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

For Juvenile myelomonocytic leukemia (Orphanet):

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

Similar variants

NF1 p.Val207Ile Uncertain significance ★★ ⚠ same residue
NF1 p.Val207Ala Uncertain significance ★ ⚠ same residue
NF1 p.Val207= Likely benign ★ same residue
NF1 c.1062+1G>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+2T>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+3A>G Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1185+1G>A Pathogenic ★★ same condition
NF1 c.1186-1G>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-val207phe (accessed [today's date]).

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