Is VPS13A p.Pro608= (c.1824A>G) pathogenic?

VPS13A p.Pro608= (c.1824A>G) is classified Likely benign in VPS13A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-23). Ultra-rare (popmax 0.0357%, eas); Associated with VPS13A-related neurodegenerative disease.

What condition is associated with VPS13A p.Pro608= (c.1824A>G)?

VPS13A p.Pro608= (c.1824A>G) is associated with VPS13A-related neurodegenerative disease (ClinVar).

How common is VPS13A p.Pro608= (c.1824A>G) in the general population?

VPS13A p.Pro608= (c.1824A>G) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

How is Choreoacanthocytosis inherited?

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

VPS13A p.Pro608=

c.1824A>G · rs750307161 · VCV697577

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Conditions

VPS13A-related neurodegenerative disease

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 -1.3	GERP -4.3
Overall
CADD	4.741	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0357% East Asian · 16/44,844 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00105% 17/1,613,894 alleles · ultra-rare exomes 14/1,461,686 · genomes 3/152,208 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,803
European (non-Finnish)	8.47e-05%	1,179,944

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.Pro608=
Coding: c.1824A>G
MANE Select: NM_033305
dbSNP: rs750307161
Type: single nucleotide variant
Location: chr9:77238310 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 608: 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 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
VPS13A c.2513-2A>T 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-pro608 (accessed [today's date]).

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