Is VPS13A p.Phe2133= (c.6399T>C) pathogenic?

VPS13A p.Phe2133= (c.6399T>C) is classified Likely benign in VPS13A (ClinVar, Single submitter, 2 submitters; last evaluated 2023-05-05). Very rare (popmax 8.7e-05%, nfe); Associated with VPS13A-related neurodegenerative disease.

What condition is associated with VPS13A p.Phe2133= (c.6399T>C)?

VPS13A p.Phe2133= (c.6399T>C) is associated with VPS13A-related neurodegenerative disease (ClinVar).

How common is VPS13A p.Phe2133= (c.6399T>C) in the general population?

VPS13A p.Phe2133= (c.6399T>C) is very rare (popmax 8.7e-05%, nfe) (gnomAD).

How is Choreoacanthocytosis inherited?

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

VPS13A p.Phe2133=

c.6399T>C · rs2131504879 · VCV1119898

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.7e-05%, nfe)

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 1.2	GERP 2.7, phastCons 1
Overall
CADD	8.976	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.7e-05% European (non-Finnish) · 1/1,149,518 alleles

Overall 6.43e-05% 1/1,554,800 alleles · very rare exomes 1/1,402,730 · genomes 0/152,070 · 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.Phe2133=
Coding: c.6399T>C
MANE Select: NM_033305
dbSNP: rs2131504879
Type: single nucleotide variant
Location: chr9:77339536 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2133: 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-phe2133 (accessed [today's date]).

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