Is ERLIN1 p.Glu92= (c.276A>G) pathogenic?

ERLIN1 p.Glu92= (c.276A>G) is classified Benign/Likely benign in ERLIN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-02). Low-frequency (popmax 1.05%, sas); Associated with hereditary spastic paraplegia 62.

What condition is associated with ERLIN1 p.Glu92= (c.276A>G)?

ERLIN1 p.Glu92= (c.276A>G) is associated with hereditary spastic paraplegia 62, hereditary spastic paraplegia (ClinVar).

How common is ERLIN1 p.Glu92= (c.276A>G) in the general population?

ERLIN1 p.Glu92= (c.276A>G) is low-frequency (popmax 1.05%, sas) (gnomAD).

How is Autosomal recessive spastic paraplegia type 62 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ERLIN1 p.Glu92=

c.276A>G · rs139168020 · VCV703858

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.05%, sas)

Conditions

hereditary spastic paraplegia 62

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 4.2	GERP 2.9, phastCons 1
Overall
CADD	11.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.05% South Asian · 905/86,046 alleles

Filtering AF 0.995% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.972%

Overall 0.0811% 1,282/1,579,918 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.05%	95
Middle Eastern	0.298%	335
Ashkenazi Jewishnot grpmax-eligible	0.107%	934
Remaining individualsnot grpmax-eligible	0.0946%	1,057
East Asian	0.0527%	1,899
European (non-Finnish)	0.0206%	4,859
Admixed American	0.0144%	6,937

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: ERLIN1
Protein: p.Glu92=
Coding: c.276A>G
MANE Select: NM_006459
dbSNP: rs139168020
Type: single nucleotide variant
Location: chr10:100178161 (GRCh38)
Gene constraint: LOEUF 1.049 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 85.49 · 4 PDB

Full ERLIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 62 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia

For Autosomal recessive spastic paraplegia type 62 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

ERLIN1 p.Ala23Thr Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Ala254Ser Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Ala258Val Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Ala292Ser Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Arg230Trp Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Arg243His Uncertain significance ★★ ⚠ same condition
ERLIN1 p.His26Asp Uncertain significance ★★ ⚠ same condition
ERLIN1 p.Ile223Thr 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/erlin1-p-glu92 (accessed [today's date]).

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