Is NF1 p.Val54= (c.162T>C) pathogenic?

NF1 p.Val54= (c.162T>C) is classified Likely benign in NF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-03-15). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with NF1 p.Val54= (c.162T>C)?

NF1 p.Val54= (c.162T>C) is associated with hereditary neoplastic syndrome, neurofibromatosis type 1 (ClinVar).

How common is NF1 p.Val54= (c.162T>C) in the general population?

NF1 p.Val54= (c.162T>C) is absent from gnomAD v4.1 (gnomAD).

NF1 p.Val54=

c.162T>C · rs876660899 · VCV234171

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.4, phastCons 1
Overall
CADD	9.583	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.Val54=
Coding: c.162T>C
MANE Select: NM_001042492
dbSNP: rs876660899
Type: single nucleotide variant
Location: chr17:31156084 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 54: 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

Also linked: neurofibromatosis type 1

Similar variants

NF1 p.Val54Phe Uncertain significance ★★ same residue
NF1 p.Val54Asp Pathogenic ★ same residue
NF1 p.Val54Ile Uncertain significance ★ same residue
NF1 p.Val54_Ile55insTer Pathogenic ★ same residue
NF1 p.Val54fs Pathogenic 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

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-val54 (accessed [today's date]).

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