Is ERLIN1 p.Pro280= (c.840G>A) pathogenic?

ERLIN1 p.Pro280= (c.840G>A) is classified Likely benign in ERLIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-04). Very rare (popmax 0.00401%, afr); Associated with hereditary spastic paraplegia 62.

What condition is associated with ERLIN1 p.Pro280= (c.840G>A)?

ERLIN1 p.Pro280= (c.840G>A) is associated with hereditary spastic paraplegia 62 (ClinVar).

How common is ERLIN1 p.Pro280= (c.840G>A) in the general population?

ERLIN1 p.Pro280= (c.840G>A) is very rare (popmax 0.00401%, afr) (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.Pro280=

c.840G>A · rs747985150 · VCV2156798

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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 -0.33	phastCons 0.12
Overall
CADD	11.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,862 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000745% 12/1,610,912 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,954
Remaining individualsnot grpmax-eligible	0.0016%	62,358
Finnishnot grpmax-eligible	0.00156%	64,010
European (non-Finnish)	0.000595%	168,166

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.Pro280=
Coding: c.840G>A
MANE Select: NM_006459
dbSNP: rs747985150
Type: single nucleotide variant
Location: chr10:100152338 (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

For Autosomal recessive spastic paraplegia type 62 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

ERLIN1 p.Pro280Leu Uncertain significance ★ ⚠ same residue
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

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-pro280 (accessed [today's date]).

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