Is ERLIN2 p.Asn106= (c.318C>T) pathogenic?

ERLIN2 p.Asn106= (c.318C>T) is classified Benign in ERLIN2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-08). Common (popmax 8.23%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Spastic paraplegia.

What condition is associated with ERLIN2 p.Asn106= (c.318C>T)?

ERLIN2 p.Asn106= (c.318C>T) is associated with Spastic paraplegia, hereditary spastic paraplegia (ClinVar).

ERLIN2 p.Asn106=

Q: How common is ERLIN2 p.Asn106= (c.318C>T) in the general population?

ERLIN2 p.Asn106= (c.318C>T) is common (popmax 8.23%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.318C>T · rs16887018 · VCV129021

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 8.23%, afr) — too common for a highly-penetrant pathogenic allele

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 1.4	GERP 2.8, phastCons 1
Overall
CADD	9.228	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.23% African / African-American · 6,171/74,978 alleles

Filtering AF 8.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.99%

Overall 0.465% 7,510/1,614,062 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.23%	12
Remaining individualsnot grpmax-eligible	0.557%	180
Admixed American	0.547%	183
Middle Eastern	0.545%	184
European (non-Finnish)	0.0492%	2,031
South Asian	0.0439%	2,277
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,700
East Asian	0.00223%	44,886

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.Asn106=
Coding: c.318C>T
MANE Select: NM_007175
dbSNP: rs16887018
Type: single nucleotide variant
Location: chr8:37744590 (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-asn106 (accessed [today's date]).

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