Is VPS13A p.Ala487Asp (c.1460C>A) pathogenic?

VPS13A p.Ala487Asp (c.1460C>A) is classified Uncertain significance in VPS13A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.227); Very rare (popmax 6.26e-05%); Associated with VPS13A-related neurodegenerative disease.

What condition is associated with VPS13A p.Ala487Asp (c.1460C>A)?

VPS13A p.Ala487Asp (c.1460C>A) is associated with VPS13A-related neurodegenerative disease (ClinVar).

How common is VPS13A p.Ala487Asp (c.1460C>A) in the general population?

VPS13A p.Ala487Asp (c.1460C>A) is very rare (popmax 6.26e-05%) (gnomAD).

How is Choreoacanthocytosis inherited?

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

What do computational predictors say about VPS13A p.Ala487Asp (c.1460C>A)?

AlphaMissense predicts likely benign (score 0.227) — an in-silico prediction, not a clinical call.

VPS13A p.Ala487Asp

c.1460C>A · VCV4063063

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.227 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.26e-05%)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

VPS13A-related neurodegenerative disease

Computational evidence

Protein change
AlphaMissense	0.227	likely benign
REVEL	0.205	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 176 kb · p 0.00021 · regional, not allelic
Overall
CADD	20.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.26e-05%

Overall 6.26e-05% 1/1,597,850 alleles · very rare exomes 1/1,445,980 · genomes 0/151,870 · joint denominator

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: VPS13A
Protein: p.Ala487Asp
Coding: c.1460C>A
MANE Select: NM_033305
Type: single nucleotide variant
Location: chr9:77228129 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 487: a UniProt-annotated variant site (in chac)

Full VPS13A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

VPS13A-related neurodegenerative disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Choreoacanthocytosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

Similar variants

VPS13A p.Ala487Gly Likely benign ★ same residue
VPS13A c.144+1G>C Pathogenic ★★ same condition
VPS13A c.1596-1G>C Pathogenic/Likely pathogenic ★★ same condition
VPS13A c.1596-2A>G Pathogenic ★★ same condition
VPS13A c.188-2A>G Likely pathogenic ★★ same condition
VPS13A c.2037+1G>A Likely pathogenic ★★ same condition
VPS13A c.2427+1G>A Likely pathogenic ★★ same condition
VPS13A c.2512+2T>C Likely pathogenic ★★ 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/vps13a-p-ala487asp (accessed [today's date]).

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