Is ERLIN2 p.Lys273= (c.819G>A) pathogenic?

ERLIN2 p.Lys273= (c.819G>A) is classified Pathogenic in ERLIN2 (ClinVar, Single submitter, 1 submitter). Very rare (popmax 8.48e-05%, nfe); Associated with hereditary spastic paraplegia 18.

What condition is associated with ERLIN2 p.Lys273= (c.819G>A)?

ERLIN2 p.Lys273= (c.819G>A) is associated with hereditary spastic paraplegia 18 (ClinVar).

How common is ERLIN2 p.Lys273= (c.819G>A) in the general population?

ERLIN2 p.Lys273= (c.819G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

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.Lys273=

c.819G>A · rs779335579 · VCV989005

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

hereditary spastic paraplegia 18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.73	donor loss · deltas
Pangolin	Δ0.79	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,694 alleles

Overall 6.84e-05% 1/1,461,450 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ERLIN2
Protein: p.Lys273=
Coding: c.819G>A
MANE Select: NM_007175
dbSNP: rs779335579
Type: single nucleotide variant
Location: chr8:37753529 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 5 PDB
Residue 273: the 'interaction with erlin1' region

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

Disease context

hereditary spastic paraplegia 18 — 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 p.Ala290Val Uncertain significance ★★ same condition
ERLIN2 c.107+2T>C Likely pathogenic ★ same condition
ERLIN2 p.Lys267Glu Pathogenic ★ same condition
ERLIN2 p.Ser293Gly Pathogenic ★ ⚠ same condition
ERLIN2 c.557+4A>C Uncertain significance ★ same condition
ERLIN2 p.Lys119Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
ERLIN2 c.499-1G>T Pathogenic same condition
ERLIN2 p.Arg180Cys 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/erlin2-p-lys273 (accessed [today's date]).

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