Is VLDLR p.Cys264= (c.792C>T) pathogenic?

VLDLR p.Cys264= (c.792C>T) is classified Conflicting classifications of pathogenicity in VLDLR (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-28). Ultra-rare (popmax 0.0552%, nfe); Associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1.

What condition is associated with VLDLR p.Cys264= (c.792C>T)?

VLDLR p.Cys264= (c.792C>T) is associated with cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 (ClinVar).

How common is VLDLR p.Cys264= (c.792C>T) in the general population?

VLDLR p.Cys264= (c.792C>T) is ultra-rare (popmax 0.0552%, nfe) (gnomAD).

How is Dysequilibrium syndrome inherited?

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

VLDLR p.Cys264=

c.792C>T · rs141850403 · VCV212564

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0552%, nfe)

Conditions

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1

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 4.1	GERP 1.1, phastCons 1
Overall
CADD	12.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0552% European (non-Finnish) · 651/1,180,048 alleles

Filtering AF 0.0516% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0502%

Overall 0.0427% 690/1,614,082 alleles · ultra-rare exomes 640/1,461,892 · genomes 50/152,190 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0552%	1,813
Remaining individualsnot grpmax-eligible	0.0384%	2,604
African / African-American	0.0133%	7,492
Admixed American	0.00833%	12,003

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: VLDLR
Protein: p.Cys264=
Coding: c.792C>T
MANE Select: NM_003383
dbSNP: rs141850403
Type: single nucleotide variant
Location: chr9:2643503 (GRCh38)
Gene constraint: LOEUF 0.828 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.12 · 27 PDB
Residue 264: the ldl-receptor class a 6 domain; a disulfide bond

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

Disease context

cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dysequilibrium syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

VLDLR c.2252-2A>C Likely pathogenic ★★ same condition
VLDLR c.449-2A>T Likely pathogenic ★★ same condition
VLDLR c.83-1G>A Pathogenic/Likely pathogenic ★★ same condition
VLDLR p.Arg279Ter Pathogenic ★★ same condition
VLDLR p.Arg301Ter Pathogenic ★★ same condition
VLDLR c.-154C>G Uncertain significance ★★ same condition
VLDLR c.-392C>T Uncertain significance ★★ same condition
VLDLR c.*48C>T 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/vldlr-p-cys264 (accessed [today's date]).

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