Is NF1 p.Val951Phe (c.2851G>T) pathogenic?

NF1 p.Val951Phe (c.2851G>T) is classified Pathogenic/Likely pathogenic in NF1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-29). AlphaMissense: likely pathogenic (0.8081); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with NF1 p.Val951Phe (c.2851G>T)?

NF1 p.Val951Phe (c.2851G>T) is associated with hereditary neoplastic syndrome, neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Val951Phe (c.2851G>T) in the general population?

NF1 p.Val951Phe (c.2851G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NF1 p.Val951Phe (c.2851G>T)?

AlphaMissense predicts likely pathogenic (score 0.8081) — an in-silico prediction, not a clinical call.

NF1 p.Val951Phe

c.2851G>T · rs1597716277 · VCV1702852

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8081 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.8081	likely pathogenic ✓ concordant with ClinVar
REVEL	0.785	moderately pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	Δ0.32	acceptor gain · deltas
Pangolin	Δ0.62	loss · gain 0.11 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 7,685 bp · p 1.1e-24 · regional, not allelic
Overall
CADD	34.0	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.Val951Phe
Coding: c.2851G>T
MANE Select: NM_001042492
dbSNP: rs1597716277
Type: single nucleotide variant
Location: chr17:31229835 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Also linked: neurofibromatosis type 1

Similar variants

NF1 p.Val951Ile Uncertain significance ★★ ⚠ same residue
NF1 p.Val951Ala Uncertain significance ★ 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
NF1 c.1062+3A>G Pathogenic/Likely pathogenic ★★ same condition
NF1 c.1062+3A>T 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-val951phe (accessed [today's date]).

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