Is ERLIN2 p.Asp69Glu (c.207T>G) pathogenic?

ERLIN2 p.Asp69Glu (c.207T>G) is classified Likely pathogenic in ERLIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-28). AlphaMissense: likely pathogenic (0.9978); Absent from gnomAD v4.1; Associated with Spastic paraplegia.

What condition is associated with ERLIN2 p.Asp69Glu (c.207T>G)?

ERLIN2 p.Asp69Glu (c.207T>G) is associated with Spastic paraplegia (ClinVar).

How common is ERLIN2 p.Asp69Glu (c.207T>G) in the general population?

ERLIN2 p.Asp69Glu (c.207T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERLIN2 p.Asp69Glu (c.207T>G)?

AlphaMissense predicts likely pathogenic (score 0.9978) — an in-silico prediction, not a clinical call.

ERLIN2 p.Asp69Glu

c.207T>G · rs2487294702 · VCV1992126

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Spastic paraplegia

Computational evidence

Protein change
AlphaMissense	0.9978	likely pathogenic ✓ concordant with ClinVar · top 10% in ERLIN2
REVEL	0.73	pathogenic-leaning
SaProt	LLR -12.65	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.9	GERP -5.2
Regional constraint	o/e 0.67	unconstrained · MANE · 6,689 bp · p 9.5e-05 · regional, not allelic
Overall
CADD	21.8	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.Asp69Glu
Coding: c.207T>G
MANE Select: NM_007175
dbSNP: rs2487294702
Type: single nucleotide variant
Location: chr8:37741789 (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.Asp69His Uncertain significance ★ ⚠ same residue
ERLIN2 p.Asp69del Uncertain significance ★ same residue
ERLIN2 p.Asp69Val Uncertain significance ★ ⚠ same residue
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

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-asp69glu (accessed [today's date]).

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