Is VPS37A p.Arg87= (c.261A>G) pathogenic?

VPS37A p.Arg87= (c.261A>G) is classified Likely benign in VPS37A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). Absent from gnomAD v4.1; Associated with hereditary spastic paraplegia 53.

What condition is associated with VPS37A p.Arg87= (c.261A>G)?

VPS37A p.Arg87= (c.261A>G) is associated with hereditary spastic paraplegia 53 (ClinVar).

How common is VPS37A p.Arg87= (c.261A>G) in the general population?

VPS37A p.Arg87= (c.261A>G) is absent from gnomAD v4.1 (gnomAD).

How is Autosomal recessive spastic paraplegia type 53 inherited?

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

VPS37A p.Arg87=

c.261A>G · rs1813659486 · VCV1971245

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary spastic paraplegia 53

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 1.1	GERP -3, phastCons 0.99
Overall
CADD	8.705	PHRED · no single calibrated threshold — expert panels disagree

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: VPS37A
Protein: p.Arg87=
Coding: c.261A>G
MANE Select: NM_152415
dbSNP: rs1813659486
Type: single nucleotide variant
Location: chr8:17268318 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 1 PDB

Full VPS37A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 53 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 53 (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

VPS37A p.Ala176Ser Uncertain significance ★★ ⚠ same condition
VPS37A p.Ala193Thr Uncertain significance ★★ ⚠ same condition
VPS37A p.Ala388Ser Uncertain significance ★★ ⚠ same condition
VPS37A p.Ala44Asp Uncertain significance ★★ ⚠ same condition
VPS37A p.Asp268Asn Uncertain significance ★★ ⚠ same condition
VPS37A p.Asp271Gly Uncertain significance ★★ ⚠ same condition
VPS37A p.Glu249Lys Uncertain significance ★★ ⚠ same condition
VPS37A p.Glu302Lys 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/vps37a-p-arg87 (accessed [today's date]).

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