Is ERLIN2 p.Ala151Val (c.452C>T) pathogenic?

ERLIN2 p.Ala151Val (c.452C>T) is classified Pathogenic/Likely pathogenic in ERLIN2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-19). AlphaMissense: likely pathogenic (0.6341); Absent from gnomAD v4.1; Associated with Spastic paraplegia.

What condition is associated with ERLIN2 p.Ala151Val (c.452C>T)?

ERLIN2 p.Ala151Val (c.452C>T) is associated with Spastic paraplegia, spastic paraplegia 18a, autosomal dominant (ClinVar).

How common is ERLIN2 p.Ala151Val (c.452C>T) in the general population?

ERLIN2 p.Ala151Val (c.452C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERLIN2 p.Ala151Val (c.452C>T)?

AlphaMissense predicts likely pathogenic (score 0.6341) — an in-silico prediction, not a clinical call.

ERLIN2 p.Ala151Val

c.452C>T · rs1554517327 · VCV458243

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6341 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Spastic paraplegia

Computational evidence

Protein change
AlphaMissense	0.6341	likely pathogenic ✓ concordant with ClinVar
REVEL	0.594	indeterminate
SaProt	LLR -12.51	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 9,452 bp · p 1e-10 · regional, not allelic
Overall
CADD	25.8	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.Ala151Val
Coding: c.452C>T
MANE Select: NM_007175
dbSNP: rs1554517327
Type: single nucleotide variant
Location: chr8:37749586 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 5 PDB
Residue 151: a UniProt-annotated variant site (in spg18a; uncertain significance)

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: spastic paraplegia 18a, autosomal dominant

Similar variants

ERLIN2 p.Val168Met 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
ERLIN2 p.Gln63Arg 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-ala151val (accessed [today's date]).

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