Is ERLIN2 p.Val82= (c.246G>A) pathogenic?

ERLIN2 p.Val82= (c.246G>A) is classified Uncertain significance in ERLIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-19). Very rare (popmax 0.00223%, eas); Associated with Spastic paraplegia.

What condition is associated with ERLIN2 p.Val82= (c.246G>A)?

ERLIN2 p.Val82= (c.246G>A) is associated with Spastic paraplegia (ClinVar).

How common is ERLIN2 p.Val82= (c.246G>A) in the general population?

ERLIN2 p.Val82= (c.246G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

ERLIN2 p.Val82=

c.246G>A · rs1802960931 · VCV1930827

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Spastic paraplegia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.29	acceptor loss, 9 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4	GERP -0.37, phastCons 1
Overall
CADD	6.828	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Overall 0.000137% 2/1,461,680 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
African / African-American	0.00133%	75,028

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.Val82=
Coding: c.246G>A
MANE Select: NM_007175
dbSNP: rs1802960931
Type: single nucleotide variant
Location: chr8:37744364 (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

Similar variants

ERLIN2 p.Ala151Val 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-val82 (accessed [today's date]).

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