Is NF1 p.Val996= (c.2988C>G) pathogenic?

NF1 p.Val996= (c.2988C>G) is classified Uncertain significance in NF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-24). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with NF1 p.Val996= (c.2988C>G)?

NF1 p.Val996= (c.2988C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is NF1 p.Val996= (c.2988C>G) in the general population?

NF1 p.Val996= (c.2988C>G) is absent from gnomAD v4.1 (gnomAD).

NF1 p.Val996=

c.2988C>G · rs2151430849 · VCV3237708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.83 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP 1.2, phastCons 1
Overall
CADD	15.36	PHRED · no single calibrated threshold — expert panels disagree

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.Val996=
Coding: c.2988C>G
MANE Select: NM_001042492
dbSNP: rs2151430849
Type: single nucleotide variant
Location: chr17:31229972 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 996: an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NF1 p.Val996Asp Uncertain significance ★★ ⚠ same residue
NF1 p.Val996Phe 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
NF1 c.1063-2A>C Pathogenic ★★ same condition
NF1 c.1063-2A>G 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-val996 (accessed [today's date]).

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