Is NF1 p.Asp2012Ala (c.6035A>C) pathogenic?

NF1 p.Asp2012Ala (c.6035A>C) is classified Uncertain significance in NF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely pathogenic (0.9909); Absent from gnomAD v4.1.

How common is NF1 p.Asp2012Ala (c.6035A>C) in the general population?

NF1 p.Asp2012Ala (c.6035A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NF1 p.Asp2012Ala (c.6035A>C)?

AlphaMissense predicts likely pathogenic (score 0.9909) — an in-silico prediction, not a clinical call.

NF1 p.Asp2012Ala

c.6035A>C · VCV4886000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9909 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.9909	likely pathogenic
REVEL	0.909	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	26.0	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

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.Asp2012Ala
Coding: c.6035A>C
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

Similar variants

NF1 p.Asp2012= Likely benign ★★ same residue
NF1 p.Asp2012Gly Uncertain significance ★ ⚠ same residue
NF1 p.Asp2012His Uncertain significance ★ ⚠ same residue
NF1 p.Asp2012Val Uncertain significance ★ ⚠ same residue
NF1 c.1062+1G>A Pathogenic/Likely pathogenic ★★ same type
NF1 c.1062+1G>C Pathogenic ★★ same type
NF1 c.1062+2T>A Pathogenic/Likely pathogenic ★★ same type
NF1 c.1062+2T>C Pathogenic/Likely pathogenic ★★ same type

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-asp2012ala (accessed [today's date]).

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