Is ERLIN2 p.Ala269= (c.807C>T) pathogenic?

ERLIN2 p.Ala269= (c.807C>T) is classified Likely benign in ERLIN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). Very rare (popmax 0.00144%, nfe); Associated with Spastic paraplegia.

What condition is associated with ERLIN2 p.Ala269= (c.807C>T)?

ERLIN2 p.Ala269= (c.807C>T) is associated with Spastic paraplegia (ClinVar).

How common is ERLIN2 p.Ala269= (c.807C>T) in the general population?

ERLIN2 p.Ala269= (c.807C>T) is very rare (popmax 0.00144%, nfe) (gnomAD).

ERLIN2 p.Ala269=

c.807C>T · rs767299905 · VCV1672899

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

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 -4.6	GERP -5.5
Overall
CADD	2.737	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,179,846 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00112% 18/1,613,748 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00144%	69,403
African / African-American	0.00133%	74,910

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.Ala269=
Coding: c.807C>T
MANE Select: NM_007175
dbSNP: rs767299905
Type: single nucleotide variant
Location: chr8:37753517 (GRCh38)
Gene constraint: LOEUF 0.703 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 5 PDB
Residue 269: the 'interaction with erlin1' region

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.Ala269Ser 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
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-ala269 (accessed [today's date]).

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