Is ERLIN2 p.Glu330fs (c.988del) pathogenic?

ERLIN2 p.Glu330fs (c.988del) is classified Likely pathogenic in ERLIN2 (ClinVar, Single submitter, 1 submitter). Associated with spastic paraplegia 18b, autosomal recessive.

What condition is associated with ERLIN2 p.Glu330fs (c.988del)?

ERLIN2 p.Glu330fs (c.988del) is associated with spastic paraplegia 18b, autosomal recessive (ClinVar).

How is Autosomal spastic paraplegia type 18 inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ERLIN2 p.Glu330fs

c.988del · VCV4759352

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

spastic paraplegia 18b, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.3	GERP -5.2

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

Variant & gene context

Gene: ERLIN2
Protein: p.Glu330fs
Coding: c.988del
MANE Select: NM_007175
Type: Deletion
Location: chr8:37754083 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 5 PDB

Full ERLIN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spastic paraplegia 18b, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal spastic paraplegia type 18 (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy

Similar variants

ERLIN2 c.819+2T>C Likely pathogenic ★ same condition
ERLIN2 p.Glu184Lys Likely pathogenic ★ same condition
ERLIN2 p.Ser324fs Likely pathogenic ★ same condition
ERLIN2 p.Ala335_Thr336del Uncertain significance ★★ same type
ERLIN2 p.Ala6fs Pathogenic ★ same type
ERLIN2 p.Asn118fs Pathogenic ★ same type
ERLIN2 p.Asn182_Tyr183insTer Likely pathogenic ★ same type
ERLIN2 p.Cys16fs 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/erlin2-p-glu330fs (accessed [today's date]).

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