Is VPS13A p.Ser992= (c.2976C>T) pathogenic?

VPS13A p.Ser992= (c.2976C>T) is classified Likely benign in VPS13A (ClinVar, Single submitter, 2 submitters; last evaluated 2021-03-24). Absent from gnomAD v4.1; Associated with VPS13A-related neurodegenerative disease.

What condition is associated with VPS13A p.Ser992= (c.2976C>T)?

VPS13A p.Ser992= (c.2976C>T) is associated with VPS13A-related neurodegenerative disease (ClinVar).

How common is VPS13A p.Ser992= (c.2976C>T) in the general population?

VPS13A p.Ser992= (c.2976C>T) is absent from gnomAD v4.1 (gnomAD).

How is Choreoacanthocytosis inherited?

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

VPS13A p.Ser992=

c.2976C>T · rs2131347014 · VCV1656325

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.33	GERP -1.6, phastCons 0.1
Overall
CADD	7.686	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: VPS13A
Protein: p.Ser992=
Coding: c.2976C>T
MANE Select: NM_033305
dbSNP: rs2131347014
Type: single nucleotide variant
Location: chr9:77282132 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 992: 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-ser992 (accessed [today's date]).

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