Is ERLIN2 p.Cys128= (c.384C>T) pathogenic?

ERLIN2 p.Cys128= (c.384C>T) is classified Conflicting classifications of pathogenicity in ERLIN2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-11-27). Rare (popmax 0.115%, mid); Associated with Spastic paraplegia.

What condition is associated with ERLIN2 p.Cys128= (c.384C>T)?

ERLIN2 p.Cys128= (c.384C>T) is associated with Spastic paraplegia, hereditary spastic paraplegia (ClinVar).

How common is ERLIN2 p.Cys128= (c.384C>T) in the general population?

ERLIN2 p.Cys128= (c.384C>T) is rare (popmax 0.115%, mid) (gnomAD).

ERLIN2 p.Cys128=

c.384C>T · rs200292614 · VCV1336315

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Conditions

Spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 2.8, phastCons 1
Overall
CADD	14.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,062 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0384%

Overall 0.00397% 64/1,614,036 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	866
African / African-American	0.0293%	3,411
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.00833%	12,004
European (non-Finnish)	0.00161%	62,100
South Asian	0.0011%	91,084

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.Cys128=
Coding: c.384C>T
MANE Select: NM_007175
dbSNP: rs200292614
Type: single nucleotide variant
Location: chr8:37744656 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia

Similar variants

ERLIN2 p.Ala151Val Pathogenic/Likely pathogenic ★★ same condition
ERLIN2 p.Gln63Lys Pathogenic/Likely pathogenic ★★ same condition
ERLIN2 c.298+5G>A Uncertain significance ★★ same condition
ERLIN2 c.819+3A>G Uncertain significance ★★ same condition
ERLIN2 p.Ala290Val Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Ala99Thr Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Asn93Asp Uncertain significance ★★ ⚠ same condition
ERLIN2 p.Gln154Pro 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-cys128 (accessed [today's date]).

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