Is NF1 p.Phe477fs (c.1431_1433delinsAT) pathogenic?

NF1 p.Phe477fs (c.14311433delinsAT) is classified Pathogenic in NF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with NF1 p.Phe477fs (c.1431_1433delinsAT)?

NF1 p.Phe477fs (c.1431_1433delinsAT) is associated with hereditary neoplastic syndrome (ClinVar).

How common is NF1 p.Phe477fs (c.1431_1433delinsAT) in the general population?

NF1 p.Phe477fs (c.1431_1433delinsAT) is absent from gnomAD (gnomAD).

NF1 p.Phe477fs

c.1431_1433delinsAT · rs2544829260 · VCV3238245

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 13 of 58
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP -0.93, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NF1
Protein: p.Phe477fs
Coding: c.1431_1433delinsAT
MANE Select: NM_001042492
dbSNP: rs2544829260
Type: Indel
Location: chr17:31214489 (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

Similar variants

NF1 p.Phe477= Benign/Likely benign ★★ same residue
NF1 p.Phe477Leu Uncertain significance ★ ⚠ same residue
NF1 p.Lys2555fs Pathogenic ★★ same condition
NF1 p.Pro678fs Pathogenic ★★ same condition
NF1 p.Ala308Phe Uncertain significance ★★ same condition
NF1 p.Asp1058Ala Uncertain significance ★★ same condition
NF1 p.Gly2499Leu Uncertain significance ★★ same condition
NF1 p.Gly309Ile Uncertain significance ★★ 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-phe477fs (accessed [today's date]).

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