Is NF1 p.Asp1069Val (c.3206A>T) pathogenic?

NF1 p.Asp1069Val (c.3206A>T) is classified Uncertain significance in NF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). AlphaMissense: likely pathogenic (0.9953); Very rare (popmax 0.000627%, nfe); Associated with neurofibromatosis type 1.

What condition is associated with NF1 p.Asp1069Val (c.3206A>T)?

NF1 p.Asp1069Val (c.3206A>T) is associated with neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Asp1069Val (c.3206A>T) in the general population?

NF1 p.Asp1069Val (c.3206A>T) is very rare (popmax 0.000627%, nfe) (gnomAD).

How is Neurofibromatosis type 1 inherited?

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

What do computational predictors say about NF1 p.Asp1069Val (c.3206A>T)?

AlphaMissense predicts likely pathogenic (score 0.9953) — an in-silico prediction, not a clinical call.

NF1 p.Asp1069Val

c.3206A>T · VCV4800744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000627%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

neurofibromatosis type 1

Computational evidence

Protein change
AlphaMissense	0.9953	likely pathogenic · top 8% in NF1
REVEL	0.742	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 7,685 bp · p 1.1e-24 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.000627% European (non-Finnish) · 3/478,360 alleles

Filtering AF 0.000167% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.6e-05%

Overall 0.00047% 3/637,914 alleles · very rare

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.Asp1069Val
Coding: c.3206A>T
MANE Select: NM_001042492
Type: single nucleotide variant
Location: chr17:31232081 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1069: 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.Asp1069Asn Uncertain significance ★ ⚠ same residue
NF1 p.Asp1069fs Pathogenic ★ same residue
NF1 p.Asp1069His Uncertain significance ★ ⚠ same residue
NF1 p.Asp1069= 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-asp1069val (accessed [today's date]).

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