Is LFNG p.Ser216fs (c.645del) pathogenic?

LFNG p.Ser216fs (c.645del) is classified Likely pathogenic in LFNG (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-09). Associated with LFNG-related disorders.

What condition is associated with LFNG p.Ser216fs (c.645del)?

LFNG p.Ser216fs (c.645del) is associated with LFNG-related disorders (ClinVar).

LFNG p.Ser216fs

c.645del · VCV4895026

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 4 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 0.41, phastCons 1

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

Variant & gene context

Gene: LFNG
Protein: p.Ser216fs
Coding: c.645del
MANE Select: NM_001040167
Type: Deletion
Location: chr7:2525476 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI 0.02 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.66

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

Disease context

LFNG-related disorders

Similar variants

LFNG p.Thr145Met Likely pathogenic ★★ same condition
LFNG p.Gln19Ter Pathogenic ★ same condition
LFNG p.Pro96fs Likely pathogenic ★ same condition
LFNG p.Glu143del Uncertain significance ★ same type
LFNG c.736-15_736-13del Likely benign ★ same type
LFNG c.822-20del Likely benign ★ same type
LFNG c.987+16_987+33del Likely benign ★ same type
LFNG p.Lys124fs Pathogenic 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-ser216fs (accessed [today's date]).

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