Is LFNG p.Pro96fs (c.270_286dup) pathogenic?

LFNG p.Pro96fs (c.270286dup) is classified Likely pathogenic in LFNG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). Associated with LFNG-related disorders.

What condition is associated with LFNG p.Pro96fs (c.270_286dup)?

LFNG p.Pro96fs (c.270_286dup) is associated with LFNG-related disorders (ClinVar).

LFNG p.Pro96fs

c.270_286dup · VCV4895021

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

LFNG-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP -1.4, phastCons 1

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

Variant & gene context

Gene: LFNG
Protein: p.Pro96fs
Coding: c.270_286dup
MANE Select: NM_001040167
Type: Duplication
Location: chr7:2520126 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI 0.02 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.66
Residue 96: the 'disordered' region

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

Disease context

LFNG-related disorders

Similar variants

LFNG p.Pro96Arg Uncertain significance ★★ ⚠ same residue
LFNG p.Thr145Met Likely pathogenic ★★ same condition
LFNG p.Gln19Ter Pathogenic ★ same condition
LFNG p.Ser216fs Likely pathogenic ★ same condition
LFNG p.Thr149fs Pathogenic ★ same type
LFNG p.Phe337_Glu338insAspMetPhe Uncertain significance ★ same type
LFNG c.482-16_482-13dup Likely benign ★ same type

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/lfng-p-pro96fs (accessed [today's date]).

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