Is NF1 p.Asp2012Val (c.6035A>T) pathogenic?

NF1 p.Asp2012Val (c.6035A>T) is classified Uncertain significance in NF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely pathogenic (0.994); Very rare (popmax 0.00133%, afr); Associated with Cardiovascular phenotype.

What condition is associated with NF1 p.Asp2012Val (c.6035A>T)?

NF1 p.Asp2012Val (c.6035A>T) is associated with Cardiovascular phenotype, hereditary neoplastic syndrome (ClinVar).

How common is NF1 p.Asp2012Val (c.6035A>T) in the general population?

NF1 p.Asp2012Val (c.6035A>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about NF1 p.Asp2012Val (c.6035A>T)?

AlphaMissense predicts likely pathogenic (score 0.994) — an in-silico prediction, not a clinical call.

NF1 p.Asp2012Val

c.6035A>T · VCV4119174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.994	likely pathogenic · top 10% in NF1
REVEL	0.876	moderately 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 9.4	GERP 0.63, phastCons 1
Regional constraint	o/e 0.41	unconstrained · MANE · 9,812 bp · p 2.1e-34 · regional, not allelic
Overall
CADD	26.3	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 0.00133% African / African-American · 1/75,014 alleles

Overall 0.000124% 2/1,614,076 alleles · very rare exomes 2/1,461,834 · genomes 0/152,242 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,014
European (non-Finnish)	8.47e-05%	1,180,008

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.Asp2012Val
Coding: c.6035A>T
MANE Select: NM_001042492
Type: single nucleotide variant
Location: chr17:31336361 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2012: a UniProt-annotated variant site (in nf1); an α-helix

Full NF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

NF1 p.Asp2012= Likely benign ★★ same residue
NF1 p.Asp2012Gly Uncertain significance ★ ⚠ same residue
NF1 p.Asp2012Ala Uncertain significance ★ ⚠ same residue
NF1 p.Asp2012His Uncertain significance ★ ⚠ same residue
NF1 c.1062+2T>C Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+3A>G Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1063-13G>A Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1063-1G>A 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-asp2012val (accessed [today's date]).

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