Is NF1 p.Phe960Val (c.2878T>G) pathogenic?

NF1 p.Phe960Val (c.2878T>G) is classified Uncertain significance in NF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-01-11). AlphaMissense: likely pathogenic (0.8481); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with NF1 p.Phe960Val (c.2878T>G)?

NF1 p.Phe960Val (c.2878T>G) is associated with Cardiovascular phenotype, hereditary neoplastic syndrome (ClinVar).

How common is NF1 p.Phe960Val (c.2878T>G) in the general population?

NF1 p.Phe960Val (c.2878T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NF1 p.Phe960Val (c.2878T>G)?

AlphaMissense predicts likely pathogenic (score 0.8481) — an in-silico prediction, not a clinical call.

NF1 p.Phe960Val

c.2878T>G · rs2151430547 · VCV1797129

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8481 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8481	likely pathogenic
REVEL	0.713	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	Δ0.31	acceptor loss, 7 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.9	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	25.9	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.Phe960Val
Coding: c.2878T>G
MANE Select: NM_001042492
dbSNP: rs2151430547
Type: single nucleotide variant
Location: chr17:31229862 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 960: 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.Phe960= Conflicting classifications of pathogenicity ★ 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
NF1 c.1185+1G>A 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-phe960val (accessed [today's date]).

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