Is VPS35 p.Asp370= (c.1110T>C) pathogenic?

VPS35 p.Asp370= (c.1110T>C) is classified Likely benign in VPS35 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). No allele count reported in gnomAD v4.1 (AN 1,614,144); Associated with Parkinson disease 17.

What condition is associated with VPS35 p.Asp370= (c.1110T>C)?

VPS35 p.Asp370= (c.1110T>C) is associated with Parkinson disease 17 (ClinVar).

How common is VPS35 p.Asp370= (c.1110T>C) in the general population?

VPS35 p.Asp370= (c.1110T>C) is no allele count reported in gnomAD v4.1 (AN 1,614,144) (gnomAD).

How is Hereditary late-onset Parkinson disease inherited?

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

VPS35 p.Asp370=

c.1110T>C · VCV3693254

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,144)

Conditions

Parkinson disease 17

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 2.6	GERP -2.5, phastCons 1
Overall
CADD	8.796	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,144). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: VPS35
Protein: p.Asp370=
Coding: c.1110T>C
MANE Select: NM_018206
Type: single nucleotide variant
Location: chr16:46674364 (GRCh38)
Gene constraint: LOEUF 0.32 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 91.40 · 14 PDB
Residue 370: an α-helix

Full VPS35 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Parkinson disease 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary late-onset Parkinson disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

VPS35 p.Asp620Asn Pathogenic ★★ same condition
VPS35 c.-19C>T Uncertain significance ★★ same condition
VPS35 c.*283C>A Uncertain significance ★★ same condition
VPS35 p.Arg138His Uncertain significance ★★ ⚠ same condition
VPS35 p.Arg284Gln Uncertain significance ★★ ⚠ same condition
VPS35 p.Arg493Cys Uncertain significance ★★ ⚠ same condition
VPS35 p.Asn37Ser Uncertain significance ★★ ⚠ same condition
VPS35 p.Asn381Ser 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/vps35-p-asp370 (accessed [today's date]).

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