Is ERLIN2 p.Lys119Arg (c.356A>G) pathogenic?

ERLIN2 p.Lys119Arg (c.356A>G) is classified Conflicting classifications of pathogenicity in ERLIN2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-09-23). AlphaMissense: likely pathogenic (0.5988); Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 18.

What condition is associated with ERLIN2 p.Lys119Arg (c.356A>G)?

ERLIN2 p.Lys119Arg (c.356A>G) is associated with hereditary spastic paraplegia 18 (ClinVar).

How common is ERLIN2 p.Lys119Arg (c.356A>G) in the general population?

ERLIN2 p.Lys119Arg (c.356A>G) is absent from gnomAD v4.1 (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.

What do computational predictors say about ERLIN2 p.Lys119Arg (c.356A>G)?

AlphaMissense predicts likely pathogenic (score 0.5988) — an in-silico prediction, not a clinical call.

ERLIN2 p.Lys119Arg

c.356A>G · rs1802974214 · VCV1032526

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary spastic paraplegia 18

Computational evidence

Protein change
AlphaMissense	0.5988	likely pathogenic
REVEL	0.663	pathogenic-leaning
SaProt	LLR -11.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.82	acceptor gain · deltas
Pangolin	Δ0.46	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.05	constrained · MANE · 46 bp · p 3.9e-05 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ERLIN2
Protein: p.Lys119Arg
Coding: c.356A>G
MANE Select: NM_007175
dbSNP: rs1802974214
Type: single nucleotide variant
Location: chr8:37744628 (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

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.Lys273= Pathogenic ★ same condition
ERLIN2 p.Ser293Gly Pathogenic ★ ⚠ same condition
ERLIN2 c.557+4A>C Uncertain significance ★ 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-lys119arg (accessed [today's date]).

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